Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review

Bomback, Andrew S.; Kshirsagar, Abhijit V.; Amamoo, M. Ahinee; Klemmer, Philip J.

doi:10.1053/j.ajkd.2007.10.040

Cited by 208 publications

(151 citation statements)

References 54 publications

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“…Our data show that these agents contribute to a significant decrease in end-of-treatment 24 h urine protein excretion, independent of effects on BP but without any impact on the decline of GFR. Bomback et al recently analyzed the effects of adding mineralocorticoid receptor blockade to RAS blockers in patients with CKD in a systematic review (42). They included both observational and RCTs and concluded that this regimen decreases proteinuria without causing any hyperkalemia or impaired renal function.…”

Section: Comparison To Other Studiesmentioning

confidence: 99%

Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease

Navaneethan

Nigwekar

Sehgal³

et al. 2009

Clinical Journal of the American Society of Nephrology

229

133

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Background and objectives: Addition of aldosterone antagonists (AA) might provide renal benefits to proteinuric chronic kidney disease (CKD) patients over and above the inhibition of renin-angiotensin system blockers (RAS). We evaluated the benefits and harms of adding selective and nonselective AA in CKD patients already on RAS.Design, setting, participants, & measurements: MEDLINE, EMBASE, and Renal Health Library were searched for relevant randomized clinical trials in adult CKD patients. Results were summarized using the random-effects model.Results: Eleven trials (991 patients) were included. In comparison to angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) plus placebo, nonselective AA along with ACEi and/or ARB significantly reduced 24 h proteinuria (seven trials, 372 patients, weighted mean difference [WMD] ؊0.80 g, 95% CI ؊1.27, ؊0.33) and BP. This did not translate into an improvement in GFR (WMD ؊0.70 ml/min/1.73m 2 , 95% CI ؊4.73, 3.34). There was a significant increase in the risk of hyperkalemia with the addition of nonselective AA to ACEi and/or ARB (relative risk 3.06, 95% CI 1.26, 7.41). In two trials, addition of selective AA to ACEi resulted in an additional reduction in 24 h proteinuria, without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available in any of the trials.Conclusions: Aldosterone antagonists reduce proteinuria in CKD patients already on ACEis and ARBs but increase the risk of hyperkalemia. Long-term effects of these agents on renal outcomes, mortality, and safety need to be established. Clin J Am Soc Nephrol 4: 542-551, 2009. doi: 10.2215 C hronic kidney disease (CKD) affects 25 to 30 million Americans and several million people across the globe in both developed and developing nations (1,2). A number of treatment options have been shown to delay the progression of kidney damage (3,4). To date, the major impact on delaying the progression of CKD and the risk of end-stage kidney disease (ESKD) has been provided by the use of renin-angiotensin system (RAS) blockers such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor-blocking agents (ARB). These agents have become standard of care in proteinuric CKD patients (5-8). Both ACEi and ARB significantly reduce proteinuria and the risk of ESKD by about 20 to 30% (9). But this is suboptimal given the higher costs and burden of ESKD (10). Thus, studies exploring interventions for traditional and nontraditional risk factors for CKD are advocated (11).Animal studies have shown that aldosterone has an independent role in the development of hypertensive nephropathy and vascular injury resulting in myocardial and renal fibrosis, and its blockade reduces proteinuria (12-16). In humans, RAS blockade with ACEi or ARB results in an incomplete suppression of serum aldosterone levels, a phenomenon known as "aldosterone escape" (17). When patients are treated with ACEi or ARB, aldosterone levels decrease during...

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Section: Comparison To Other Studiesmentioning

confidence: 99%

Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease

Navaneethan

Nigwekar

Sehgal³

et al. 2009

Clinical Journal of the American Society of Nephrology

229

133

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“…Although the role of MRAs in patients with ejection fraction greater than 35% is unclear,2, 3 they may benefit patients with comorbid hypertension, diabetes mellitus, or renal insufficiency. MRAs can be used for blood pressure management regardless of heart failure status, and addition of an MRA to angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker therapy reduces proteinuria in patients with chronic kidney disease and diabetic nephropathy and can delay progression of renal dysfunction 3, 4, 5, 6, 7, 8, 9, 10…”

Section: Introductionmentioning

confidence: 99%

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Cooper

Lippmann

Greiner

et al. 2017

JAHA

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BackgroundPerceived risks of hyperkalemia and acute renal insufficiency may limit use of mineralocorticoid receptor antagonist (MRA) therapy in patients with heart failure, especially those with diabetes mellitus or chronic kidney disease.Methods and ResultsUsing clinical registry data linked to Medicare claims, we analyzed patients hospitalized with heart failure between 2005 and 2013 with a history of diabetes mellitus or chronic kidney disease. We stratified patients by MRA use at discharge. We used inverse probability–weighted proportional hazards models to assess associations between MRA therapy and 30‐day, 1‐year, and 3‐year mortality, all‐cause readmission, and readmission for heart failure, hyperkalemia, and acute renal insufficiency. We performed interaction analyses for differential effects on 3‐year outcomes for reduced, borderline, and preserved ejection fraction. Of 16 848 patients, 12.3% received MRA therapy at discharge. Higher serum creatinine was associated with lower odds of MRA use (odds ratio, 0.66; 95% confidence interval, 0.61–0.71); serum potassium was not (odds ratio, 1.00; 95% confidence interval, 0.90–1.11). There was no mortality difference between groups. MRA therapy was associated with greater risks of readmission for hyperkalemia and acute renal insufficiency and lower risks of long‐term all‐cause readmission. Patients on MRA therapy with borderline or preserved ejection fraction had greater risks of readmission for hyperkalemia (P=0.02) and acute renal insufficiency (P<0.001); patients with reduced ejection fraction did not.ConclusionsAmong patients with heart failure and diabetes mellitus or chronic kidney disease, MRA use was associated with lower risk of all‐cause readmission despite greater risk of hyperkalemia and acute renal insufficiency.

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“…All strategies reduce proteinuria compared with single-agent therapy (5)(6)(7)(8)(9)(10)(11), but hyperkalemia is a risk (12,13). Regimens including an ACE inhibitor and ARB or either drug and DRI are not recommended not only because of the risk of hyperkalemia but also because of renal failure and hypotension, which were seen in large clinical trials (14,15).…”

Section: Introductionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.Design, setting, participants, & measurements In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.Results Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P,0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P,0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.Conclusion Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

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Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review

Cited by 208 publications

References 54 publications

Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease

Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

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