Nephrology

A 49-year-old man developed nephrotic-range proteinuria (urine protein–creatinine ratio 4.1 g/g), and primary membranous nephropathy was diagnosed by kidney biopsy. He declined therapy apart from angiotensin receptor blockade.

Five months after undergoing the biopsy, he presented to the emergency room with marked dyspnea, cough, and epigastric discomfort. His blood pressure was 160/100 mm Hg, heart rate 95 beats/minute, and oxygen saturation by pulse oximetry 97% at rest on ambient air, decreasing to 92% with ambulation.

Initial laboratory testing results were as follows:

• Sodium 135 mmol/L (reference range 136–144)
• Potassium 3.9 mmol/L (3.7–5.1)
• Chloride 104 mmol/L (97–105)
• Bicarbonate 21 mmol/L (22–30)
• Blood urea nitrogen 14 mg/dL (9–24)
• Serum creatinine 1.1 mg/dL (0.73–1.22)
• Albumin 2.1 g/dL (3.4–4.9).

Urinalysis revealed the following:

• 5 red blood cells per high-power field, compared with 1 to 2 previously
• 3+ proteinuria
• Urine protein–creatinine ratio 11 g/g
• No glucosuria.

Electrocardiography revealed normal sinus rhythm without ischemic changes. Chest radiography did not show consolidation.

At 7 months after the thrombotic event, there was no evidence of residual renal vein thrombosis on magnetic resonance venography, and at 14 months his serum creatinine level was 0.9 mg/dL, albumin 4.0 g/dL, and urine protein–creatinine ratio 0.8 g/g.

RENAL VEIN THROMBOSIS: RISK FACTORS AND CLINICAL FEATURES

Severe hypoalbuminemia in the setting of nephrotic syndrome due to membranous neph­ropathy is associated with the highest risk of venous thromboembolic events, with renal vein thrombus being the classic complication.¹ Venous thromboembolic events also occur in other nephrotic syndromes, albeit at a lower frequency.²

Venous thromboembolic events are estimated to occur in 7% to 33% of patients with membranous glomerulopathy, with albumin levels less than 2.8 g/dL considered a notable risk factor.^1,2

While often a chronic complication, acute renal vein thrombosis may present with flank pain and hematuria.³ In our patient, the dramatic increase in proteinuria and possibly the increase in hematuria suggested renal vein thrombosis. Proximal tubular dysfunction, such as glucosuria, can be seen on occasion.

DIAGNOSIS AND TREATMENT

Screening asymptomatic patients for renal vein thrombosis is not recommended, and the decision to start prophylactic anticoagulation must be individualized.⁴

Although renal venography historically was the gold standard test to diagnose renal vein thrombosis, it has been replaced by noninvasive imaging such as computed tomography and magnetic resonance venography.

While anticoagulation remains the treatment of choice, catheter-directed thrombectomy or surgical thrombectomy can be considered for some patients with acute renal vein thrombosis.⁵

A 49-year-old man developed nephrotic-range proteinuria (urine protein–creatinine ratio 4.1 g/g), and primary membranous nephropathy was diagnosed by kidney biopsy. He declined therapy apart from angiotensin receptor blockade.

Five months after undergoing the biopsy, he presented to the emergency room with marked dyspnea, cough, and epigastric discomfort. His blood pressure was 160/100 mm Hg, heart rate 95 beats/minute, and oxygen saturation by pulse oximetry 97% at rest on ambient air, decreasing to 92% with ambulation.

Initial laboratory testing results were as follows:

• Sodium 135 mmol/L (reference range 136–144)
• Potassium 3.9 mmol/L (3.7–5.1)
• Chloride 104 mmol/L (97–105)
• Bicarbonate 21 mmol/L (22–30)
• Blood urea nitrogen 14 mg/dL (9–24)
• Serum creatinine 1.1 mg/dL (0.73–1.22)
• Albumin 2.1 g/dL (3.4–4.9).

Urinalysis revealed the following:

• 5 red blood cells per high-power field, compared with 1 to 2 previously
• 3+ proteinuria
• Urine protein–creatinine ratio 11 g/g
• No glucosuria.

Electrocardiography revealed normal sinus rhythm without ischemic changes. Chest radiography did not show consolidation.

At 7 months after the thrombotic event, there was no evidence of residual renal vein thrombosis on magnetic resonance venography, and at 14 months his serum creatinine level was 0.9 mg/dL, albumin 4.0 g/dL, and urine protein–creatinine ratio 0.8 g/g.

RENAL VEIN THROMBOSIS: RISK FACTORS AND CLINICAL FEATURES

Severe hypoalbuminemia in the setting of nephrotic syndrome due to membranous neph­ropathy is associated with the highest risk of venous thromboembolic events, with renal vein thrombus being the classic complication.¹ Venous thromboembolic events also occur in other nephrotic syndromes, albeit at a lower frequency.²

Venous thromboembolic events are estimated to occur in 7% to 33% of patients with membranous glomerulopathy, with albumin levels less than 2.8 g/dL considered a notable risk factor.^1,2

While often a chronic complication, acute renal vein thrombosis may present with flank pain and hematuria.³ In our patient, the dramatic increase in proteinuria and possibly the increase in hematuria suggested renal vein thrombosis. Proximal tubular dysfunction, such as glucosuria, can be seen on occasion.

DIAGNOSIS AND TREATMENT

Screening asymptomatic patients for renal vein thrombosis is not recommended, and the decision to start prophylactic anticoagulation must be individualized.⁴

Although renal venography historically was the gold standard test to diagnose renal vein thrombosis, it has been replaced by noninvasive imaging such as computed tomography and magnetic resonance venography.

While anticoagulation remains the treatment of choice, catheter-directed thrombectomy or surgical thrombectomy can be considered for some patients with acute renal vein thrombosis.⁵

A 49-year-old man developed nephrotic-range proteinuria (urine protein–creatinine ratio 4.1 g/g), and primary membranous nephropathy was diagnosed by kidney biopsy. He declined therapy apart from angiotensin receptor blockade.

Five months after undergoing the biopsy, he presented to the emergency room with marked dyspnea, cough, and epigastric discomfort. His blood pressure was 160/100 mm Hg, heart rate 95 beats/minute, and oxygen saturation by pulse oximetry 97% at rest on ambient air, decreasing to 92% with ambulation.

Initial laboratory testing results were as follows:

• Sodium 135 mmol/L (reference range 136–144)
• Potassium 3.9 mmol/L (3.7–5.1)
• Chloride 104 mmol/L (97–105)
• Bicarbonate 21 mmol/L (22–30)
• Blood urea nitrogen 14 mg/dL (9–24)
• Serum creatinine 1.1 mg/dL (0.73–1.22)
• Albumin 2.1 g/dL (3.4–4.9).

Urinalysis revealed the following:

• 5 red blood cells per high-power field, compared with 1 to 2 previously
• 3+ proteinuria
• Urine protein–creatinine ratio 11 g/g
• No glucosuria.

Electrocardiography revealed normal sinus rhythm without ischemic changes. Chest radiography did not show consolidation.

At 7 months after the thrombotic event, there was no evidence of residual renal vein thrombosis on magnetic resonance venography, and at 14 months his serum creatinine level was 0.9 mg/dL, albumin 4.0 g/dL, and urine protein–creatinine ratio 0.8 g/g.

RENAL VEIN THROMBOSIS: RISK FACTORS AND CLINICAL FEATURES

Severe hypoalbuminemia in the setting of nephrotic syndrome due to membranous neph­ropathy is associated with the highest risk of venous thromboembolic events, with renal vein thrombus being the classic complication.¹ Venous thromboembolic events also occur in other nephrotic syndromes, albeit at a lower frequency.²

Venous thromboembolic events are estimated to occur in 7% to 33% of patients with membranous glomerulopathy, with albumin levels less than 2.8 g/dL considered a notable risk factor.^1,2

While often a chronic complication, acute renal vein thrombosis may present with flank pain and hematuria.³ In our patient, the dramatic increase in proteinuria and possibly the increase in hematuria suggested renal vein thrombosis. Proximal tubular dysfunction, such as glucosuria, can be seen on occasion.

DIAGNOSIS AND TREATMENT

Screening asymptomatic patients for renal vein thrombosis is not recommended, and the decision to start prophylactic anticoagulation must be individualized.⁴

Although renal venography historically was the gold standard test to diagnose renal vein thrombosis, it has been replaced by noninvasive imaging such as computed tomography and magnetic resonance venography.

While anticoagulation remains the treatment of choice, catheter-directed thrombectomy or surgical thrombectomy can be considered for some patients with acute renal vein thrombosis.⁵

Here are 5 articles from the November issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term NSAIDs appear safe for high-risk patients

To take the posttest, go to: https://bit.ly/2PgXKGx
Expires October 8, 2019

2. Chronic liver disease raises death risk in pneumonia patients

To take the posttest, go to: https://bit.ly/2NPSXXA
Expires October 8, 2019

3. Half of outpatient antibiotics prescribed with no infectious disease code

To take the posttest, go to: https://bit.ly/2pWEWxU
Expires October 6, 2019

4. Secondary fractures in older men spike soon after first, but exercise may help

To take the posttest, go to: https://bit.ly/2OCNl8A
Expires October 3, 2019

5. Consider ART for younger endometriosis patients

To take the posttest, go to: https://bit.ly/2NO1Sc4
Expires October 5, 2019

Here are 5 articles from the November issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term NSAIDs appear safe for high-risk patients

To take the posttest, go to: https://bit.ly/2PgXKGx
Expires October 8, 2019

2. Chronic liver disease raises death risk in pneumonia patients

To take the posttest, go to: https://bit.ly/2NPSXXA
Expires October 8, 2019

3. Half of outpatient antibiotics prescribed with no infectious disease code

To take the posttest, go to: https://bit.ly/2pWEWxU
Expires October 6, 2019

4. Secondary fractures in older men spike soon after first, but exercise may help

To take the posttest, go to: https://bit.ly/2OCNl8A
Expires October 3, 2019

5. Consider ART for younger endometriosis patients

To take the posttest, go to: https://bit.ly/2NO1Sc4
Expires October 5, 2019

Here are 5 articles from the November issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term NSAIDs appear safe for high-risk patients

To take the posttest, go to: https://bit.ly/2PgXKGx
Expires October 8, 2019

2. Chronic liver disease raises death risk in pneumonia patients

To take the posttest, go to: https://bit.ly/2NPSXXA
Expires October 8, 2019

3. Half of outpatient antibiotics prescribed with no infectious disease code

To take the posttest, go to: https://bit.ly/2pWEWxU
Expires October 6, 2019

4. Secondary fractures in older men spike soon after first, but exercise may help

To take the posttest, go to: https://bit.ly/2OCNl8A
Expires October 3, 2019

5. Consider ART for younger endometriosis patients

To take the posttest, go to: https://bit.ly/2NO1Sc4
Expires October 5, 2019

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

Both age and type of insurance are significantly associated with greater delays in treatment of febrile urinary tract infections (UTIs), even after adjustment for confounders, according to a report in the Journal of Pediatrics.

Zizulhalmi/Thinkstock

Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.

In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.

The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.

The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.

One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.

This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.

[email protected]

SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.

This article was updated 10/24/18.

The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.

decade3d/Thinkstock

The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.

Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.

The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.

Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”

Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.

“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.

The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.

decade3d/Thinkstock

The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.

Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.

The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.

Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”

Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.

“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.

The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.

decade3d/Thinkstock

The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.

Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.

The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.

Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”

Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.

“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.

Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.