Nephrology

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds. 

The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.

“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.) 
 

CKD Severity Equals Thinner Retinas

“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.

The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm³ vs 8.73 ± .36 mm³ (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m² compared with control volunteers at 97 ± 14 mL/min/1.73 m².

The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring. 

The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m² in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.

The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
 

Exploring the Kidney-Eye Connection 

The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said. 

“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said. 

“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.” 

OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.

“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”

The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease. 

“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”

Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.

The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.

A version of this article first appeared on Medscape.com.

Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds. 

The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.

“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.) 
 

CKD Severity Equals Thinner Retinas

“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.

The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm³ vs 8.73 ± .36 mm³ (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m² compared with control volunteers at 97 ± 14 mL/min/1.73 m².

The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring. 

The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m² in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.

The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
 

Exploring the Kidney-Eye Connection 

The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said. 

“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said. 

“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.” 

OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.

“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”

The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease. 

“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”

Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.

The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.

A version of this article first appeared on Medscape.com.

Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds. 

The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.

“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.) 
 

CKD Severity Equals Thinner Retinas

“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.

The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm³ vs 8.73 ± .36 mm³ (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m² compared with control volunteers at 97 ± 14 mL/min/1.73 m².

The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring. 

The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m² in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.

The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
 

Exploring the Kidney-Eye Connection 

The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said. 

“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said. 

“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.” 

OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.

“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”

The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease. 

“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”

Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.

The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.

A version of this article first appeared on Medscape.com.

TOPLINE

Being overweight or obese in adolescence significantly increases the risk of developing early chronic kidney disease (CKD) in young adulthood, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.

METHODOLOGY

• The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
• The mean age at study entry was 17.2 and 54.5% were male.
• Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m² or higher.
• The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
• Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.

TAKEAWAY

• With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
• Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
• In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
• For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
• For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.

IN PRACTICE

“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report. 

“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.

“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”

SOURCE

The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.

LIMITATIONS

The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.

DISCLOSURES

Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE

Being overweight or obese in adolescence significantly increases the risk of developing early chronic kidney disease (CKD) in young adulthood, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.

METHODOLOGY

• The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
• The mean age at study entry was 17.2 and 54.5% were male.
• Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m² or higher.
• The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
• Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.

TAKEAWAY

• With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
• Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
• In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
• For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
• For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.

IN PRACTICE

“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report. 

“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.

“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”

SOURCE

The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.

LIMITATIONS

The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.

DISCLOSURES

Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE

Being overweight or obese in adolescence significantly increases the risk of developing early chronic kidney disease (CKD) in young adulthood, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.

METHODOLOGY

• The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
• The mean age at study entry was 17.2 and 54.5% were male.
• Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m² or higher.
• The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
• Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.

TAKEAWAY

• With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
• Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
• In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
• For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
• For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.

IN PRACTICE

“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report. 

“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.

“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”

SOURCE

The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.

LIMITATIONS

The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.

DISCLOSURES

Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).

Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.

The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.

“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”

Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”

The updates are outlined below.
 

Expanded Access to HCV-Positive Kidneys

While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.

In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.

Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.

“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”

Dr. Rastogi agreed that this recommendation is the most impactful update.

“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”

For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.

In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.

“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”

This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
 

Sofosbuvir Given the Green Light

Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m², including those receiving dialysis.

This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.

“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
 

Loosened Biopsy Requirements

Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.

“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.

If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
 

Individualizing Immunosuppressive Therapy

Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.

Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
 

More Work Is Needed

Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.

“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”

The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.

The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).

Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.

The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.

“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”

Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”

The updates are outlined below.
 

Expanded Access to HCV-Positive Kidneys

While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.

In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.

Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.

“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”

Dr. Rastogi agreed that this recommendation is the most impactful update.

“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”

For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.

In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.

“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”

This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
 

Sofosbuvir Given the Green Light

Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m², including those receiving dialysis.

This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.

“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
 

Loosened Biopsy Requirements

Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.

“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.

If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
 

Individualizing Immunosuppressive Therapy

Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.

Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
 

More Work Is Needed

Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.

“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”

The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.

The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).

Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.

The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.

“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”

Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”

The updates are outlined below.
 

Expanded Access to HCV-Positive Kidneys

While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.

In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.

Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.

“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”

Dr. Rastogi agreed that this recommendation is the most impactful update.

“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”

For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.

In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.

“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”

This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
 

Sofosbuvir Given the Green Light

Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m², including those receiving dialysis.

This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.

“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
 

Loosened Biopsy Requirements

Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.

“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.

If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
 

Individualizing Immunosuppressive Therapy

Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.

Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
 

More Work Is Needed

Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.

“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”

The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.