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When to Discontinue RAAS Therapy in CKD Patients
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.