Nephrology

NEW ORLEANS – Insulin glargine 300 U/mL provided comparable glycemic control to that seen with insulin glargine 100 U/mL and consistently reduced the risk of nocturnal hypoglycemia in patients with type 2 diabetes, regardless of their renal function, results from a large post hoc meta-analysis showed.

The EDITION I, II, and III studies showed that over a period of 6 months, Gla-300 provided comparable glycemic control to Gla-100 with less hypoglycemia in patients with type 2 diabetes. However, “renal impairment increases the risk of hypoglycemia in people with type 2 diabetes, and may limit glucose-lowering therapy options,” Javier Escalada, M.D., said at the annual scientific sessions of the American Diabetes Association. “Therefore, it may be more challenging to manage diabetes in this population than in people with normal renal function.”

Dr. Escalada of the department of endocrinology and nutrition at Clinic University of Navarra, Pamplona, Spain, and his associates set out to investigate the impact of renal function on hemoglobin A_1c reduction and hypoglycemia in a post hoc meta-analysis of 2,468 patients aged 18 years and older with type 2 diabetes who were treated with Gla-300 or Gla-100 for 6 months in the EDITION I, II, and III studies. Treatment consisted of once-daily evening doses of Gla-300 or Gla-100 titrated to a fasting self-measured plasma glucose of 80-100 mg/dL. Patients were classified by their renal function as having moderate loss (30 to less than 60 mL/min per 1.73 m³; 399 patients), mild loss (60 to less than 90; 1,386 patients), or normal function (at least 90; 683 patients).

Outcomes of interest were change in HbA_1c from baseline to month 6, and the percentages of patients achieving an HbA_1c target of lower than 7.0% and lower than 7.5% at month 6. The researchers also assessed the cumulative number of hypoglycemic events, the relative risk of at least one confirmed or severe hypoglycemic event, and the nocturnal and at any time event rate per participant year.

Slightly more than half of participants (56%) had a baseline estimated glomerular filtration rate of 60 to less than 90 mL/min per 1.73 m³. Dr. Escalada reported that noninferiority for HbA1c reduction was shown for Gla-300 and Gla-100 regardless of renal function, and that evidence of heterogeneity of treatment effect across subgroups was observed (P = .46). However, the risk of confirmed or severe hypoglycemia was significantly lower for nocturnal events in the Gla-300 group, compared with the Gla-100 group (30% vs. 40% overall, respectively), while the risk of anytime hypoglycemia events in a 24-hour period was comparable to or lower in the Gla-300 group, compared with the Gla-100 group. Renal function did not affect the lower rate of nocturnal or anytime hypoglycemia. “Severe hypoglycemia was rare, and renal function did not affect the rate of severe events,” he said.

The trial was sponsored by Sanofi. Dr. Escalada disclosed that he is a member of the advisory panel for Sanofi and for Merck Sharp & Dohme. He is also a member of the speakers bureau for both companies as well as for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

[email protected]

NEW ORLEANS – Insulin glargine 300 U/mL provided comparable glycemic control to that seen with insulin glargine 100 U/mL and consistently reduced the risk of nocturnal hypoglycemia in patients with type 2 diabetes, regardless of their renal function, results from a large post hoc meta-analysis showed.

The EDITION I, II, and III studies showed that over a period of 6 months, Gla-300 provided comparable glycemic control to Gla-100 with less hypoglycemia in patients with type 2 diabetes. However, “renal impairment increases the risk of hypoglycemia in people with type 2 diabetes, and may limit glucose-lowering therapy options,” Javier Escalada, M.D., said at the annual scientific sessions of the American Diabetes Association. “Therefore, it may be more challenging to manage diabetes in this population than in people with normal renal function.”

Dr. Escalada of the department of endocrinology and nutrition at Clinic University of Navarra, Pamplona, Spain, and his associates set out to investigate the impact of renal function on hemoglobin A_1c reduction and hypoglycemia in a post hoc meta-analysis of 2,468 patients aged 18 years and older with type 2 diabetes who were treated with Gla-300 or Gla-100 for 6 months in the EDITION I, II, and III studies. Treatment consisted of once-daily evening doses of Gla-300 or Gla-100 titrated to a fasting self-measured plasma glucose of 80-100 mg/dL. Patients were classified by their renal function as having moderate loss (30 to less than 60 mL/min per 1.73 m³; 399 patients), mild loss (60 to less than 90; 1,386 patients), or normal function (at least 90; 683 patients).

Outcomes of interest were change in HbA_1c from baseline to month 6, and the percentages of patients achieving an HbA_1c target of lower than 7.0% and lower than 7.5% at month 6. The researchers also assessed the cumulative number of hypoglycemic events, the relative risk of at least one confirmed or severe hypoglycemic event, and the nocturnal and at any time event rate per participant year.

Slightly more than half of participants (56%) had a baseline estimated glomerular filtration rate of 60 to less than 90 mL/min per 1.73 m³. Dr. Escalada reported that noninferiority for HbA1c reduction was shown for Gla-300 and Gla-100 regardless of renal function, and that evidence of heterogeneity of treatment effect across subgroups was observed (P = .46). However, the risk of confirmed or severe hypoglycemia was significantly lower for nocturnal events in the Gla-300 group, compared with the Gla-100 group (30% vs. 40% overall, respectively), while the risk of anytime hypoglycemia events in a 24-hour period was comparable to or lower in the Gla-300 group, compared with the Gla-100 group. Renal function did not affect the lower rate of nocturnal or anytime hypoglycemia. “Severe hypoglycemia was rare, and renal function did not affect the rate of severe events,” he said.

The trial was sponsored by Sanofi. Dr. Escalada disclosed that he is a member of the advisory panel for Sanofi and for Merck Sharp & Dohme. He is also a member of the speakers bureau for both companies as well as for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

[email protected]

NEW ORLEANS – Insulin glargine 300 U/mL provided comparable glycemic control to that seen with insulin glargine 100 U/mL and consistently reduced the risk of nocturnal hypoglycemia in patients with type 2 diabetes, regardless of their renal function, results from a large post hoc meta-analysis showed.

The EDITION I, II, and III studies showed that over a period of 6 months, Gla-300 provided comparable glycemic control to Gla-100 with less hypoglycemia in patients with type 2 diabetes. However, “renal impairment increases the risk of hypoglycemia in people with type 2 diabetes, and may limit glucose-lowering therapy options,” Javier Escalada, M.D., said at the annual scientific sessions of the American Diabetes Association. “Therefore, it may be more challenging to manage diabetes in this population than in people with normal renal function.”

Dr. Escalada of the department of endocrinology and nutrition at Clinic University of Navarra, Pamplona, Spain, and his associates set out to investigate the impact of renal function on hemoglobin A_1c reduction and hypoglycemia in a post hoc meta-analysis of 2,468 patients aged 18 years and older with type 2 diabetes who were treated with Gla-300 or Gla-100 for 6 months in the EDITION I, II, and III studies. Treatment consisted of once-daily evening doses of Gla-300 or Gla-100 titrated to a fasting self-measured plasma glucose of 80-100 mg/dL. Patients were classified by their renal function as having moderate loss (30 to less than 60 mL/min per 1.73 m³; 399 patients), mild loss (60 to less than 90; 1,386 patients), or normal function (at least 90; 683 patients).

Outcomes of interest were change in HbA_1c from baseline to month 6, and the percentages of patients achieving an HbA_1c target of lower than 7.0% and lower than 7.5% at month 6. The researchers also assessed the cumulative number of hypoglycemic events, the relative risk of at least one confirmed or severe hypoglycemic event, and the nocturnal and at any time event rate per participant year.

Slightly more than half of participants (56%) had a baseline estimated glomerular filtration rate of 60 to less than 90 mL/min per 1.73 m³. Dr. Escalada reported that noninferiority for HbA1c reduction was shown for Gla-300 and Gla-100 regardless of renal function, and that evidence of heterogeneity of treatment effect across subgroups was observed (P = .46). However, the risk of confirmed or severe hypoglycemia was significantly lower for nocturnal events in the Gla-300 group, compared with the Gla-100 group (30% vs. 40% overall, respectively), while the risk of anytime hypoglycemia events in a 24-hour period was comparable to or lower in the Gla-300 group, compared with the Gla-100 group. Renal function did not affect the lower rate of nocturnal or anytime hypoglycemia. “Severe hypoglycemia was rare, and renal function did not affect the rate of severe events,” he said.

The trial was sponsored by Sanofi. Dr. Escalada disclosed that he is a member of the advisory panel for Sanofi and for Merck Sharp & Dohme. He is also a member of the speakers bureau for both companies as well as for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

[email protected]

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

In Reply: We thank the readers for their important and insightful comments and questions.

Dr. Yilmaz raises the point that there was no mandate in the SPRINT trial to preferentially use any specific class of antihypertensive medications in either group. However, there was greater use of all drug classes (including diuretics and renin-angiotensin-aldosterone blockers) in the intensive-treatment group.¹ (This information was included as a supplementary appendix in the main paper, and as Table 1 in our review.) Could this have contributed to the primary cardiovascular outcome benefit seen in the intensive-therapy group, largely driven by a decreased incidence of heart failure, or could it even have masked the symptoms of heart failure rather than preventing it^2,3? While this is plausible, since the SPRINT trial was designed as a “treat to target” study and not as an antihypertensive medication efficacy study, it is difficult to conclusively answer the question of potential pleiotropic effects of antihypertensive medications influencing the trial results. The authors did not comment on this in the main paper, and we agree that further analysis would be helpful in exploring this important question.

Dr. Edwards raises the question whether antihypertensive therapy confers additional cardiovascular benefit over aggressive use of statins. Statin use in the SPRINT cohort (both intensive and standard groups) was low at baseline, despite this being a population at high cardiovascular risk.¹ It is unclear whether treatment practices pertaining to lipid management could have changed during the course of the trial in participants within the SPRINT cohort, particularly after the new lipid guidelines were published. The recently published HOPE-3 trial indicated cardiovascular benefit with statins used as a primary prevention strategy in older persons with intermediate cardiovascular risk.^4,5 Notably, outcomes with combination therapy in this trial using a statin plus antihypertensive therapy were not significantly better than with statin alone, except in the subgroup of participants who were in the upper third of systolic blood pressure levels, where combination appeared to benefit more. This study, of course, was done in a population with lower cardiovascular risk than in SPRINT, and the antihypertensive medications used (candesartan and hydrochlorothiazide) were not at maximal doses. There is also a question of whether use of chlorthalidone in HOPE-3 may have been more effective.

We agree with Dr. Edwards that this is an important question that merits further exploration, especially in the broader context of treatment based on cardiovascular risk.

In Reply: We thank the readers for their important and insightful comments and questions.

Dr. Yilmaz raises the point that there was no mandate in the SPRINT trial to preferentially use any specific class of antihypertensive medications in either group. However, there was greater use of all drug classes (including diuretics and renin-angiotensin-aldosterone blockers) in the intensive-treatment group.¹ (This information was included as a supplementary appendix in the main paper, and as Table 1 in our review.) Could this have contributed to the primary cardiovascular outcome benefit seen in the intensive-therapy group, largely driven by a decreased incidence of heart failure, or could it even have masked the symptoms of heart failure rather than preventing it^2,3? While this is plausible, since the SPRINT trial was designed as a “treat to target” study and not as an antihypertensive medication efficacy study, it is difficult to conclusively answer the question of potential pleiotropic effects of antihypertensive medications influencing the trial results. The authors did not comment on this in the main paper, and we agree that further analysis would be helpful in exploring this important question.

Dr. Edwards raises the question whether antihypertensive therapy confers additional cardiovascular benefit over aggressive use of statins. Statin use in the SPRINT cohort (both intensive and standard groups) was low at baseline, despite this being a population at high cardiovascular risk.¹ It is unclear whether treatment practices pertaining to lipid management could have changed during the course of the trial in participants within the SPRINT cohort, particularly after the new lipid guidelines were published. The recently published HOPE-3 trial indicated cardiovascular benefit with statins used as a primary prevention strategy in older persons with intermediate cardiovascular risk.^4,5 Notably, outcomes with combination therapy in this trial using a statin plus antihypertensive therapy were not significantly better than with statin alone, except in the subgroup of participants who were in the upper third of systolic blood pressure levels, where combination appeared to benefit more. This study, of course, was done in a population with lower cardiovascular risk than in SPRINT, and the antihypertensive medications used (candesartan and hydrochlorothiazide) were not at maximal doses. There is also a question of whether use of chlorthalidone in HOPE-3 may have been more effective.

We agree with Dr. Edwards that this is an important question that merits further exploration, especially in the broader context of treatment based on cardiovascular risk.

In Reply: We thank the readers for their important and insightful comments and questions.

Dr. Yilmaz raises the point that there was no mandate in the SPRINT trial to preferentially use any specific class of antihypertensive medications in either group. However, there was greater use of all drug classes (including diuretics and renin-angiotensin-aldosterone blockers) in the intensive-treatment group.¹ (This information was included as a supplementary appendix in the main paper, and as Table 1 in our review.) Could this have contributed to the primary cardiovascular outcome benefit seen in the intensive-therapy group, largely driven by a decreased incidence of heart failure, or could it even have masked the symptoms of heart failure rather than preventing it^2,3? While this is plausible, since the SPRINT trial was designed as a “treat to target” study and not as an antihypertensive medication efficacy study, it is difficult to conclusively answer the question of potential pleiotropic effects of antihypertensive medications influencing the trial results. The authors did not comment on this in the main paper, and we agree that further analysis would be helpful in exploring this important question.

Dr. Edwards raises the question whether antihypertensive therapy confers additional cardiovascular benefit over aggressive use of statins. Statin use in the SPRINT cohort (both intensive and standard groups) was low at baseline, despite this being a population at high cardiovascular risk.¹ It is unclear whether treatment practices pertaining to lipid management could have changed during the course of the trial in participants within the SPRINT cohort, particularly after the new lipid guidelines were published. The recently published HOPE-3 trial indicated cardiovascular benefit with statins used as a primary prevention strategy in older persons with intermediate cardiovascular risk.^4,5 Notably, outcomes with combination therapy in this trial using a statin plus antihypertensive therapy were not significantly better than with statin alone, except in the subgroup of participants who were in the upper third of systolic blood pressure levels, where combination appeared to benefit more. This study, of course, was done in a population with lower cardiovascular risk than in SPRINT, and the antihypertensive medications used (candesartan and hydrochlorothiazide) were not at maximal doses. There is also a question of whether use of chlorthalidone in HOPE-3 may have been more effective.

We agree with Dr. Edwards that this is an important question that merits further exploration, especially in the broader context of treatment based on cardiovascular risk.

LONDON – Updated management recommendations for patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis from the European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association aim to provide clinicians with reliable guidance on the best approach to treatment.

The update, presented at the European Congress of Rheumatology and recently published online in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Jun 23. doi:10.1136/annrheumdis-2016-209133), reassessed items in the 2009 recommendations for the management of primary systemic vasculitis and focused only on the management of ANCA-associated vasculitis (AAV), according to recommendations task force member Dr. Max Yates.

“In the past 5 years, 1,691 papers have been published on primary systemic vasculitis in internal medicine, rheumatology, and nephrology journals. Together with the licensing of rituximab for AAV, it was an opportune time to update the recommendations with an AAV focus,” Dr. Yates explained. The revised guidance is based on a systematic literature review from January 2007 to February 2015, focusing in particular on specific items that needed updating, such as the importance of ANCA testing and biopsy in diagnosis and follow-up, disease staging at diagnosis, the choices for remission-induction and remission-maintenance therapies, and the drug choices for relapsing and refractory disease. The task force considered for the first time the choice of immunosuppressive drugs and biologic agents (principally rituximab) and immunologic monitoring. They identified patient education as another priority.

“These updated recommendations provide a framework of practice and should apply to the majority of patients with AAV,” added Dr. Yates, who is a clinical fellow at Norwich Medical School at the University of East Anglia and works in the department of rheumatology at the Norfolk and Norwich (England) University Hospital.

The 22-member task force included rheumatologists, internists, nephrologists, a clinical immunologist, an otorhinolaryngologist, a chest physician, an ophthalmologist, a vasculitis nurse, and a patient with vasculitis from 11 countries in Europe and the United States. The task force was convened by rheumatologist Dr. Chetan Mukhtyar of the Norfolk and Norwich University Hospital on behalf of EULAR and by vasculitis and renal specialist Dr. David Jayne of Addenbrooke’s Hospital in Cambridge (England) on behalf of the European Renal Association-European Dialysis and Transplant Association.

The recommendations now contain one single, simple overarching principle, Dr. Mukhtyar said at the congress. That is, the need for shared decision making between the patient and the clinician. This principle is also included as the first point in many of the other recently updated EULAR recommendations on the management of rheumatic diseases.

Both previous and updated versions of the vasculitis recommendations contain 15 recommendations, with some changed and others combined. One key recommendation is about who should treat patients with AAV; it states that patients “should be managed in close collaboration with, or at, centers of expertise,” Dr. Mukhtyar said.“Patients with ANCA-associated vasculitis have often very complex presentations that involve several different specialties, and it is always worthwhile that these patients are looked after by people who commonly see them, because these are rare conditions,” he observed.

Deciding when to perform a biopsy is also covered, with the recommendation being that it can be used to establish a new diagnosis and to further evaluate cases of suspected relapsing vasculitis. “When do you do a biopsy?” Dr. Mukhtyar asked. “Well, every time you can, every time it is clinically feasible,” he suggested.

As for treatment, there are different recommendations depending on whether the aim is to induce or maintain remission and whether there has been a major relapse. In patients with organ- or life-threatening disease, for example, the advice is to use glucocorticoids and either cyclophosphamide or rituximab to induce remission, Dr. Mukhtyar said. The specific dosing or administration of glucocorticoids is not specified as this will depend on the clinical situation, but the advice is to taper down when possible, somewhere between month 3 and 5.

For remission induction in less severe (non–organ threatening) disease, the recommendation is to use glucocorticoids plus either methotrexate or mycophenolate mofetil. Situations when methotrexate or mycophenolate mofetil should and should not be used are specified, notably when cyclophosphamide or rituximab are not available or are contraindicated.

For maintenance of remission, the task force advised using low-dose glucocorticoids plus azathioprine, rituximab, methotrexate, or mycophenolate mofetil.

Guidance on when to use plasma exchange is given for patients with severe disease and options following failure of remission-induction therapy, and when to switch therapy is also covered.

There are also several follow-up recommendations, such as the periodic assessment of cardiovascular risk, and patient-focused recommendations on awareness of the nature, benefits, and risks of therapy. 

The recommendations should provide clinicians with reliable guidance on the best approach to treating AAV, according to Dr. Yates. “From the patients’ point of view, these recommendations should provide useful insight into which treatments they are likely to be offered and when. They also emphasize that as a patient, you should have a voice in your treatment and if you have any questions or concerns, be sure to speak with your specialist.” 

Dr. Yates and Dr. Mukhtyar did not report having any relevant disclosures.

LONDON – Updated management recommendations for patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis from the European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association aim to provide clinicians with reliable guidance on the best approach to treatment.

The update, presented at the European Congress of Rheumatology and recently published online in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Jun 23. doi:10.1136/annrheumdis-2016-209133), reassessed items in the 2009 recommendations for the management of primary systemic vasculitis and focused only on the management of ANCA-associated vasculitis (AAV), according to recommendations task force member Dr. Max Yates.

“In the past 5 years, 1,691 papers have been published on primary systemic vasculitis in internal medicine, rheumatology, and nephrology journals. Together with the licensing of rituximab for AAV, it was an opportune time to update the recommendations with an AAV focus,” Dr. Yates explained. The revised guidance is based on a systematic literature review from January 2007 to February 2015, focusing in particular on specific items that needed updating, such as the importance of ANCA testing and biopsy in diagnosis and follow-up, disease staging at diagnosis, the choices for remission-induction and remission-maintenance therapies, and the drug choices for relapsing and refractory disease. The task force considered for the first time the choice of immunosuppressive drugs and biologic agents (principally rituximab) and immunologic monitoring. They identified patient education as another priority.

“These updated recommendations provide a framework of practice and should apply to the majority of patients with AAV,” added Dr. Yates, who is a clinical fellow at Norwich Medical School at the University of East Anglia and works in the department of rheumatology at the Norfolk and Norwich (England) University Hospital.

The 22-member task force included rheumatologists, internists, nephrologists, a clinical immunologist, an otorhinolaryngologist, a chest physician, an ophthalmologist, a vasculitis nurse, and a patient with vasculitis from 11 countries in Europe and the United States. The task force was convened by rheumatologist Dr. Chetan Mukhtyar of the Norfolk and Norwich University Hospital on behalf of EULAR and by vasculitis and renal specialist Dr. David Jayne of Addenbrooke’s Hospital in Cambridge (England) on behalf of the European Renal Association-European Dialysis and Transplant Association.

The recommendations now contain one single, simple overarching principle, Dr. Mukhtyar said at the congress. That is, the need for shared decision making between the patient and the clinician. This principle is also included as the first point in many of the other recently updated EULAR recommendations on the management of rheumatic diseases.

Both previous and updated versions of the vasculitis recommendations contain 15 recommendations, with some changed and others combined. One key recommendation is about who should treat patients with AAV; it states that patients “should be managed in close collaboration with, or at, centers of expertise,” Dr. Mukhtyar said.“Patients with ANCA-associated vasculitis have often very complex presentations that involve several different specialties, and it is always worthwhile that these patients are looked after by people who commonly see them, because these are rare conditions,” he observed.

Deciding when to perform a biopsy is also covered, with the recommendation being that it can be used to establish a new diagnosis and to further evaluate cases of suspected relapsing vasculitis. “When do you do a biopsy?” Dr. Mukhtyar asked. “Well, every time you can, every time it is clinically feasible,” he suggested.

As for treatment, there are different recommendations depending on whether the aim is to induce or maintain remission and whether there has been a major relapse. In patients with organ- or life-threatening disease, for example, the advice is to use glucocorticoids and either cyclophosphamide or rituximab to induce remission, Dr. Mukhtyar said. The specific dosing or administration of glucocorticoids is not specified as this will depend on the clinical situation, but the advice is to taper down when possible, somewhere between month 3 and 5.

For remission induction in less severe (non–organ threatening) disease, the recommendation is to use glucocorticoids plus either methotrexate or mycophenolate mofetil. Situations when methotrexate or mycophenolate mofetil should and should not be used are specified, notably when cyclophosphamide or rituximab are not available or are contraindicated.

For maintenance of remission, the task force advised using low-dose glucocorticoids plus azathioprine, rituximab, methotrexate, or mycophenolate mofetil.

Guidance on when to use plasma exchange is given for patients with severe disease and options following failure of remission-induction therapy, and when to switch therapy is also covered.

There are also several follow-up recommendations, such as the periodic assessment of cardiovascular risk, and patient-focused recommendations on awareness of the nature, benefits, and risks of therapy. 

The recommendations should provide clinicians with reliable guidance on the best approach to treating AAV, according to Dr. Yates. “From the patients’ point of view, these recommendations should provide useful insight into which treatments they are likely to be offered and when. They also emphasize that as a patient, you should have a voice in your treatment and if you have any questions or concerns, be sure to speak with your specialist.” 

Dr. Yates and Dr. Mukhtyar did not report having any relevant disclosures.

LONDON – Updated management recommendations for patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis from the European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association aim to provide clinicians with reliable guidance on the best approach to treatment.

The update, presented at the European Congress of Rheumatology and recently published online in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Jun 23. doi:10.1136/annrheumdis-2016-209133), reassessed items in the 2009 recommendations for the management of primary systemic vasculitis and focused only on the management of ANCA-associated vasculitis (AAV), according to recommendations task force member Dr. Max Yates.

“In the past 5 years, 1,691 papers have been published on primary systemic vasculitis in internal medicine, rheumatology, and nephrology journals. Together with the licensing of rituximab for AAV, it was an opportune time to update the recommendations with an AAV focus,” Dr. Yates explained. The revised guidance is based on a systematic literature review from January 2007 to February 2015, focusing in particular on specific items that needed updating, such as the importance of ANCA testing and biopsy in diagnosis and follow-up, disease staging at diagnosis, the choices for remission-induction and remission-maintenance therapies, and the drug choices for relapsing and refractory disease. The task force considered for the first time the choice of immunosuppressive drugs and biologic agents (principally rituximab) and immunologic monitoring. They identified patient education as another priority.

“These updated recommendations provide a framework of practice and should apply to the majority of patients with AAV,” added Dr. Yates, who is a clinical fellow at Norwich Medical School at the University of East Anglia and works in the department of rheumatology at the Norfolk and Norwich (England) University Hospital.

The 22-member task force included rheumatologists, internists, nephrologists, a clinical immunologist, an otorhinolaryngologist, a chest physician, an ophthalmologist, a vasculitis nurse, and a patient with vasculitis from 11 countries in Europe and the United States. The task force was convened by rheumatologist Dr. Chetan Mukhtyar of the Norfolk and Norwich University Hospital on behalf of EULAR and by vasculitis and renal specialist Dr. David Jayne of Addenbrooke’s Hospital in Cambridge (England) on behalf of the European Renal Association-European Dialysis and Transplant Association.

The recommendations now contain one single, simple overarching principle, Dr. Mukhtyar said at the congress. That is, the need for shared decision making between the patient and the clinician. This principle is also included as the first point in many of the other recently updated EULAR recommendations on the management of rheumatic diseases.

Both previous and updated versions of the vasculitis recommendations contain 15 recommendations, with some changed and others combined. One key recommendation is about who should treat patients with AAV; it states that patients “should be managed in close collaboration with, or at, centers of expertise,” Dr. Mukhtyar said.“Patients with ANCA-associated vasculitis have often very complex presentations that involve several different specialties, and it is always worthwhile that these patients are looked after by people who commonly see them, because these are rare conditions,” he observed.

Deciding when to perform a biopsy is also covered, with the recommendation being that it can be used to establish a new diagnosis and to further evaluate cases of suspected relapsing vasculitis. “When do you do a biopsy?” Dr. Mukhtyar asked. “Well, every time you can, every time it is clinically feasible,” he suggested.

As for treatment, there are different recommendations depending on whether the aim is to induce or maintain remission and whether there has been a major relapse. In patients with organ- or life-threatening disease, for example, the advice is to use glucocorticoids and either cyclophosphamide or rituximab to induce remission, Dr. Mukhtyar said. The specific dosing or administration of glucocorticoids is not specified as this will depend on the clinical situation, but the advice is to taper down when possible, somewhere between month 3 and 5.

For remission induction in less severe (non–organ threatening) disease, the recommendation is to use glucocorticoids plus either methotrexate or mycophenolate mofetil. Situations when methotrexate or mycophenolate mofetil should and should not be used are specified, notably when cyclophosphamide or rituximab are not available or are contraindicated.

For maintenance of remission, the task force advised using low-dose glucocorticoids plus azathioprine, rituximab, methotrexate, or mycophenolate mofetil.

Guidance on when to use plasma exchange is given for patients with severe disease and options following failure of remission-induction therapy, and when to switch therapy is also covered.

There are also several follow-up recommendations, such as the periodic assessment of cardiovascular risk, and patient-focused recommendations on awareness of the nature, benefits, and risks of therapy. 

The recommendations should provide clinicians with reliable guidance on the best approach to treating AAV, according to Dr. Yates. “From the patients’ point of view, these recommendations should provide useful insight into which treatments they are likely to be offered and when. They also emphasize that as a patient, you should have a voice in your treatment and if you have any questions or concerns, be sure to speak with your specialist.” 

Dr. Yates and Dr. Mukhtyar did not report having any relevant disclosures.

Q) One of my diabetic patients read about finerenone in The New York Times. Apparently, it’s the “newest cure for albuminuria”! Is this just hype, or do the trials on this medication really show progress against kidney disease? Should I buy stock in the company?

Albuminuria (> 500 mg/d) associated with diabetic nephropathy and other glomerular diseases increases patient risk for chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD). Reduction of albuminuria has been shown to slow the progression of CKD.

Renin-angiotensin-aldosterone system (RAAS) blockers, such as ACE inhibitors or angiotensin receptor blockers, are considered firstline therapy to reduce albuminuria. Additional treatment modalities include diuretics, nondihydropyridine calcium channel blockers, ß-blockers, and aldosterone antagonist therapy. Limiting dietary sodium helps control blood pressure, thus slowing disease progression. In addition, some studies show that limiting phosphorus and protein (for the latter, intake of no more than 0.7 g/kg ideal body weight per day) may slow the progression of CKD. Unfortunately, despite these interventions, patients may still advance to ESRD.¹

The aldosterone and steroidal mineralocorticoid receptor antagonists (MRA) spironolactone and eplerenone have been found to reduce albuminuria when used in conjunction with RAAS blockade. However, patients using this combination are up to eight times more likely to experience hyperkalemia—a serious, potentially life-threatening adverse condition—than those not using an MRA.² The presence of hyperkalemia requires discontinuation of the RAAS blocker and the MRA, at least temporarily.

Finerenone, a nonsteroidal MRA with “greater receptor selectivity than spironolactone and better receptor affinity than eplerenone in vitro,” is in phase III trials for the treatment of systolic and diastolic dysfunction and reduction of morbidity and mortality associated with heart failure.² One study has already demonstrated that finerenone (5 to 10 mg/d) is at least as effective as spironolactone (25 mg/d) for heart failure patients.³

The Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) found that finerenone at 10 to 20 mg/d was superior to spironolactone and eplerenone, partly due to the decreased incidence of hyperkalemia. However, it should be noted that the lower incidence of hyperkalemia may be attributable to the fact that 66% of the study participants had an estimated glomerular filtration rate (eGFR) greater than 60 mL/min and that potential participants with a serum potassium level of more than 4.8 mEq/L were not included in the study.²

Additional research is needed to confirm superiority of finerenone over spironolactone and eplerenone, in conjunction with RAAS blockers, in the treatment of albuminuria and hyperkalemia. Including subjects with lower eGFR (such as patients with stage IV CKD who are at higher risk for hyperkalemia) would give a better indication of finerenone’s efficacy. In the meantime, it’s probably too soon to corner the market on this stock! —SEB

Susan E. Brown, MS, ARNP, ACNP-BC, CCRN
Great River Nephrology, West Burlington, Iowa

References
1. Parikh SV, Haddad NJ, Hebert LA. Retarding progression of kidney disease. In: Johnson RJ, Feehally J, Floege J, eds. Comprehensive Clinical Nephrology. 5th ed. Philadelphia, PA: Saunders; 2015:931-940.
2. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884-894.
3. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist, protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69-78.

Q) One of my diabetic patients read about finerenone in The New York Times. Apparently, it’s the “newest cure for albuminuria”! Is this just hype, or do the trials on this medication really show progress against kidney disease? Should I buy stock in the company?

Albuminuria (> 500 mg/d) associated with diabetic nephropathy and other glomerular diseases increases patient risk for chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD). Reduction of albuminuria has been shown to slow the progression of CKD.

Renin-angiotensin-aldosterone system (RAAS) blockers, such as ACE inhibitors or angiotensin receptor blockers, are considered firstline therapy to reduce albuminuria. Additional treatment modalities include diuretics, nondihydropyridine calcium channel blockers, ß-blockers, and aldosterone antagonist therapy. Limiting dietary sodium helps control blood pressure, thus slowing disease progression. In addition, some studies show that limiting phosphorus and protein (for the latter, intake of no more than 0.7 g/kg ideal body weight per day) may slow the progression of CKD. Unfortunately, despite these interventions, patients may still advance to ESRD.¹

The aldosterone and steroidal mineralocorticoid receptor antagonists (MRA) spironolactone and eplerenone have been found to reduce albuminuria when used in conjunction with RAAS blockade. However, patients using this combination are up to eight times more likely to experience hyperkalemia—a serious, potentially life-threatening adverse condition—than those not using an MRA.² The presence of hyperkalemia requires discontinuation of the RAAS blocker and the MRA, at least temporarily.

Finerenone, a nonsteroidal MRA with “greater receptor selectivity than spironolactone and better receptor affinity than eplerenone in vitro,” is in phase III trials for the treatment of systolic and diastolic dysfunction and reduction of morbidity and mortality associated with heart failure.² One study has already demonstrated that finerenone (5 to 10 mg/d) is at least as effective as spironolactone (25 mg/d) for heart failure patients.³

The Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) found that finerenone at 10 to 20 mg/d was superior to spironolactone and eplerenone, partly due to the decreased incidence of hyperkalemia. However, it should be noted that the lower incidence of hyperkalemia may be attributable to the fact that 66% of the study participants had an estimated glomerular filtration rate (eGFR) greater than 60 mL/min and that potential participants with a serum potassium level of more than 4.8 mEq/L were not included in the study.²

Additional research is needed to confirm superiority of finerenone over spironolactone and eplerenone, in conjunction with RAAS blockers, in the treatment of albuminuria and hyperkalemia. Including subjects with lower eGFR (such as patients with stage IV CKD who are at higher risk for hyperkalemia) would give a better indication of finerenone’s efficacy. In the meantime, it’s probably too soon to corner the market on this stock! —SEB

Susan E. Brown, MS, ARNP, ACNP-BC, CCRN
Great River Nephrology, West Burlington, Iowa

References
1. Parikh SV, Haddad NJ, Hebert LA. Retarding progression of kidney disease. In: Johnson RJ, Feehally J, Floege J, eds. Comprehensive Clinical Nephrology. 5th ed. Philadelphia, PA: Saunders; 2015:931-940.
2. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884-894.
3. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist, protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69-78.

Q) One of my diabetic patients read about finerenone in The New York Times. Apparently, it’s the “newest cure for albuminuria”! Is this just hype, or do the trials on this medication really show progress against kidney disease? Should I buy stock in the company?

Albuminuria (> 500 mg/d) associated with diabetic nephropathy and other glomerular diseases increases patient risk for chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD). Reduction of albuminuria has been shown to slow the progression of CKD.

Renin-angiotensin-aldosterone system (RAAS) blockers, such as ACE inhibitors or angiotensin receptor blockers, are considered firstline therapy to reduce albuminuria. Additional treatment modalities include diuretics, nondihydropyridine calcium channel blockers, ß-blockers, and aldosterone antagonist therapy. Limiting dietary sodium helps control blood pressure, thus slowing disease progression. In addition, some studies show that limiting phosphorus and protein (for the latter, intake of no more than 0.7 g/kg ideal body weight per day) may slow the progression of CKD. Unfortunately, despite these interventions, patients may still advance to ESRD.¹

The aldosterone and steroidal mineralocorticoid receptor antagonists (MRA) spironolactone and eplerenone have been found to reduce albuminuria when used in conjunction with RAAS blockade. However, patients using this combination are up to eight times more likely to experience hyperkalemia—a serious, potentially life-threatening adverse condition—than those not using an MRA.² The presence of hyperkalemia requires discontinuation of the RAAS blocker and the MRA, at least temporarily.

Finerenone, a nonsteroidal MRA with “greater receptor selectivity than spironolactone and better receptor affinity than eplerenone in vitro,” is in phase III trials for the treatment of systolic and diastolic dysfunction and reduction of morbidity and mortality associated with heart failure.² One study has already demonstrated that finerenone (5 to 10 mg/d) is at least as effective as spironolactone (25 mg/d) for heart failure patients.³

The Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) found that finerenone at 10 to 20 mg/d was superior to spironolactone and eplerenone, partly due to the decreased incidence of hyperkalemia. However, it should be noted that the lower incidence of hyperkalemia may be attributable to the fact that 66% of the study participants had an estimated glomerular filtration rate (eGFR) greater than 60 mL/min and that potential participants with a serum potassium level of more than 4.8 mEq/L were not included in the study.²

Additional research is needed to confirm superiority of finerenone over spironolactone and eplerenone, in conjunction with RAAS blockers, in the treatment of albuminuria and hyperkalemia. Including subjects with lower eGFR (such as patients with stage IV CKD who are at higher risk for hyperkalemia) would give a better indication of finerenone’s efficacy. In the meantime, it’s probably too soon to corner the market on this stock! —SEB

Susan E. Brown, MS, ARNP, ACNP-BC, CCRN
Great River Nephrology, West Burlington, Iowa

References
1. Parikh SV, Haddad NJ, Hebert LA. Retarding progression of kidney disease. In: Johnson RJ, Feehally J, Floege J, eds. Comprehensive Clinical Nephrology. 5th ed. Philadelphia, PA: Saunders; 2015:931-940.
2. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884-894.
3. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist, protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69-78.

Q) I see patients with diabetes, hypertension, chronic kidney disease (CKD), obesity ... often all within the same patient! I keep hearing that the DASH diet is best for these patients. Is this true? Do you have any suggestions (or handouts) for teaching good eating habits in a 15-minute office visit?

It is always nice to focus on what patients can do, rather than what they can’t. Patients with diabetes, kidney disease, heart disease, and obesity hear a lot of “can’t” messages, making “can” messages particularly important to emphasize.

Healthy diets for diabetes, heart, and kidney patients include foods low in trans and saturated fats and sodium. Not all CKD patients are required to follow a low-potassium diet; dietary restrictions are based on laboratory values, medications, and other factors. As we know, adding an ACE inhibitor or an angiotensin receptor blocker (ARB) to the treatment regimen can cause an elevation in serum potassium.

For adults with CKD, it is recommended that sodium intake be restricted to < 2,000 mg/d.⁴ And in this population, salt substitutes are not recommended, since they often contain large amounts of potassium chloride, which increases risk for hyperkalemia.⁵ Other ­spices (eg, garlic, pepper, lemon) are better substitutes for salt.

The late Paul Prudhomme, an award-winning chef from New Orleans, struggled with obesity and health issues for years. He developed wonderful, kidney-friendly spices free of salt and potassium. His line of spices, Magic Seasoning Blends, is sold in many grocery stores. You can recommend them without worry.

Studies have shown that the usual Western diet (which features an abundance of processed foods, fats, and sugars) contributes to kidney disease.⁶ The DASH (Dietary Approaches to Stop Hypertension) diet, developed by cardio experts, replaces these foods with healthier alternatives.

Recent research has shown that the DASH diet does, in fact, slow the progression of kidney disease.⁷ It also lowers blood pressure and decreases kidney stone formation, which are risk factors for kidney disease.

So, the DASH diet is protective for your patients (from both a kidney and a cardiac standpoint)—but how do you explain this in a 15-minute office visit?

Here are a few quick tips:
• Increase fruit and vegetable intake to include all colors on your plate (and no, tan is not really a color)
• If you eat meat, the cooking method should start with “B” (ie, bake, boil, broil, barbeque [without salty sauce]) ... Note that “fried” does not start with “B”!
• Use a smaller plate and you will not eat as much
• Use technology in your favor. There are great apps and downloads you can recommend (see Table). —CC

Christine Corbett, MSN, APRN, FNP-BC, CNN-NP
Kansas City Veterans Affairs, Kansas City, Missouri

References
4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;(3):1-150.
5. National Kidney Disease Education Program. Potassium: tips for people with chronic kidney disease (CKD). www.niddk.nih.gov/health-information/health-communication-programs/nkdep/a-z/nutrition-potassium/Documents/nutrition-potassium-508.pdf. Accessed June 20, 2016.
6. Odermatt A. The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease. Am J Physiol Renal Physiol. 2011;301(5):F919-F931.
7. Steiber A. DASH-style diet effective in preventing, delaying CKD progression. Renal and Urology News. 2012.

Q) I see patients with diabetes, hypertension, chronic kidney disease (CKD), obesity ... often all within the same patient! I keep hearing that the DASH diet is best for these patients. Is this true? Do you have any suggestions (or handouts) for teaching good eating habits in a 15-minute office visit?

It is always nice to focus on what patients can do, rather than what they can’t. Patients with diabetes, kidney disease, heart disease, and obesity hear a lot of “can’t” messages, making “can” messages particularly important to emphasize.

Healthy diets for diabetes, heart, and kidney patients include foods low in trans and saturated fats and sodium. Not all CKD patients are required to follow a low-potassium diet; dietary restrictions are based on laboratory values, medications, and other factors. As we know, adding an ACE inhibitor or an angiotensin receptor blocker (ARB) to the treatment regimen can cause an elevation in serum potassium.

For adults with CKD, it is recommended that sodium intake be restricted to < 2,000 mg/d.⁴ And in this population, salt substitutes are not recommended, since they often contain large amounts of potassium chloride, which increases risk for hyperkalemia.⁵ Other ­spices (eg, garlic, pepper, lemon) are better substitutes for salt.

The late Paul Prudhomme, an award-winning chef from New Orleans, struggled with obesity and health issues for years. He developed wonderful, kidney-friendly spices free of salt and potassium. His line of spices, Magic Seasoning Blends, is sold in many grocery stores. You can recommend them without worry.

Studies have shown that the usual Western diet (which features an abundance of processed foods, fats, and sugars) contributes to kidney disease.⁶ The DASH (Dietary Approaches to Stop Hypertension) diet, developed by cardio experts, replaces these foods with healthier alternatives.

Recent research has shown that the DASH diet does, in fact, slow the progression of kidney disease.⁷ It also lowers blood pressure and decreases kidney stone formation, which are risk factors for kidney disease.

So, the DASH diet is protective for your patients (from both a kidney and a cardiac standpoint)—but how do you explain this in a 15-minute office visit?

Here are a few quick tips:
• Increase fruit and vegetable intake to include all colors on your plate (and no, tan is not really a color)
• If you eat meat, the cooking method should start with “B” (ie, bake, boil, broil, barbeque [without salty sauce]) ... Note that “fried” does not start with “B”!
• Use a smaller plate and you will not eat as much
• Use technology in your favor. There are great apps and downloads you can recommend (see Table). —CC

Christine Corbett, MSN, APRN, FNP-BC, CNN-NP
Kansas City Veterans Affairs, Kansas City, Missouri

References
4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;(3):1-150.
5. National Kidney Disease Education Program. Potassium: tips for people with chronic kidney disease (CKD). www.niddk.nih.gov/health-information/health-communication-programs/nkdep/a-z/nutrition-potassium/Documents/nutrition-potassium-508.pdf. Accessed June 20, 2016.
6. Odermatt A. The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease. Am J Physiol Renal Physiol. 2011;301(5):F919-F931.
7. Steiber A. DASH-style diet effective in preventing, delaying CKD progression. Renal and Urology News. 2012.

Q) I see patients with diabetes, hypertension, chronic kidney disease (CKD), obesity ... often all within the same patient! I keep hearing that the DASH diet is best for these patients. Is this true? Do you have any suggestions (or handouts) for teaching good eating habits in a 15-minute office visit?

It is always nice to focus on what patients can do, rather than what they can’t. Patients with diabetes, kidney disease, heart disease, and obesity hear a lot of “can’t” messages, making “can” messages particularly important to emphasize.

Healthy diets for diabetes, heart, and kidney patients include foods low in trans and saturated fats and sodium. Not all CKD patients are required to follow a low-potassium diet; dietary restrictions are based on laboratory values, medications, and other factors. As we know, adding an ACE inhibitor or an angiotensin receptor blocker (ARB) to the treatment regimen can cause an elevation in serum potassium.

For adults with CKD, it is recommended that sodium intake be restricted to < 2,000 mg/d.⁴ And in this population, salt substitutes are not recommended, since they often contain large amounts of potassium chloride, which increases risk for hyperkalemia.⁵ Other ­spices (eg, garlic, pepper, lemon) are better substitutes for salt.

The late Paul Prudhomme, an award-winning chef from New Orleans, struggled with obesity and health issues for years. He developed wonderful, kidney-friendly spices free of salt and potassium. His line of spices, Magic Seasoning Blends, is sold in many grocery stores. You can recommend them without worry.

Studies have shown that the usual Western diet (which features an abundance of processed foods, fats, and sugars) contributes to kidney disease.⁶ The DASH (Dietary Approaches to Stop Hypertension) diet, developed by cardio experts, replaces these foods with healthier alternatives.

Recent research has shown that the DASH diet does, in fact, slow the progression of kidney disease.⁷ It also lowers blood pressure and decreases kidney stone formation, which are risk factors for kidney disease.

So, the DASH diet is protective for your patients (from both a kidney and a cardiac standpoint)—but how do you explain this in a 15-minute office visit?

Here are a few quick tips:
• Increase fruit and vegetable intake to include all colors on your plate (and no, tan is not really a color)
• If you eat meat, the cooking method should start with “B” (ie, bake, boil, broil, barbeque [without salty sauce]) ... Note that “fried” does not start with “B”!
• Use a smaller plate and you will not eat as much
• Use technology in your favor. There are great apps and downloads you can recommend (see Table). —CC

Christine Corbett, MSN, APRN, FNP-BC, CNN-NP
Kansas City Veterans Affairs, Kansas City, Missouri

References
4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;(3):1-150.
5. National Kidney Disease Education Program. Potassium: tips for people with chronic kidney disease (CKD). www.niddk.nih.gov/health-information/health-communication-programs/nkdep/a-z/nutrition-potassium/Documents/nutrition-potassium-508.pdf. Accessed June 20, 2016.
6. Odermatt A. The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease. Am J Physiol Renal Physiol. 2011;301(5):F919-F931.
7. Steiber A. DASH-style diet effective in preventing, delaying CKD progression. Renal and Urology News. 2012.

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.

“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.

©picsfive/Fotolia

The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.

Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m²) or stage 5 (eGFR, less than 15 mL/min per 1.73 m² or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).

All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.

Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.

“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”

AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.

A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.

“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.

©picsfive/Fotolia

The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.

Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m²) or stage 5 (eGFR, less than 15 mL/min per 1.73 m² or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).

All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.

Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.

“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”

AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.

A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.

“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.

©picsfive/Fotolia

The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.

Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m²) or stage 5 (eGFR, less than 15 mL/min per 1.73 m² or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).

All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.

Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.

“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”

AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.