Studies have shown the progression of kidney disease may be slowed by angiotensin receptor blockers (ARBs) by reducing blood pressure, reducing proteinuria, improving renal blood flow, and improving interglomerular pressure due to the vasodilatory effects of ARBs.1-6
The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) recommends that an ARB or angiotensin converting enzyme inhibitor (ACEI) be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours.7 The guideline also suggests an ARB or ACEI be used in diabetic adults with CKD and urine albumin excretion 30 to 300 mg/24 hours.
The 2017 ACC/AHA Hypertension Guidelines say that ACEIs are a reasonable antihypertensive treatment for adults with CKD to slow kidney disease progression [Moderate recommendation (Level B-R)].8 This guideline recommends ARBs as an alternative if ACEIs are not tolerated. [Weak recommendation (Level C-EO)]. The JNC8 guideline also recommends that adults with chronic kidney disease should include an ARB or an ACEI as part of their antihypertensive treatment to improve kidney outcomes. [Moderate recommendation (Grade B)]9
A 2015 network meta-analysis found ARB monotherapy significantly reduced progression to end-stage renal disease in people with diabetes compared to placebo (odds ratio [OR] 0.77, 95% confidence interval [CI] [0.65 – 0.92]).1 Combination therapy with ARB and ACEI was superior (OR 0.62, 95% CI [0.43 – 0.90]), but this combination has some risk of increased hyperkalemia and acute kidney injury.
A 2008 meta-analysis of 49 studies with 6,181 patients with or without diabetes and with microalbuminuria or proteinuria examined the effect of ARBs versus placebo and alternative treatments on proteinuria.6 Over one to four months, ARBs lowered proteinuria compared with placebo (ratio of means 0.57, 95% CI [0.47 – 0.68]) and over 5 to 12 months (ratio of means 0.66, CI [0.63 – 0.69]).
Irbesartan and losartan are FDA approved to treat diabetic nephropathy in people with type 2 diabetes and hypertension.10
Periodic renal function monitoring is recommended for patients taking ARBs. 11-19 Drugs that inhibit the renin-angiotensin system, such as ARBs, can cause changes in renal function including acute renal failure. Patients whose renal function may depend on the activity of the renin-angiotensin system include those with renal artery stenosis, CKD, severe heart failure, or volume depletion. They may be at higher risk of developing oliguria, progressive azotemia, or acute renal failure when taking an ARB. Doctors should consider withholding or discontinuing treatment in patients who develop a clinically significant decrease in renal function on an ARB.
References
- Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385 (9982): 2047-2056.
- Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345 (12): 861-869.
- Woo KT, Choong HL, Wong KS, et al. Aliskiren and losartan trial in non-diabetic chronic kidney disease. J Renin Angiotensin Aldosterone Syst 2014; 15 (4): 515-522.
- Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345 (12): 851-860.
- Kobori H, Mori H, Masaki T, Nishiyama A. Angiotensin II blockade and renal protection. Curr Pharm Des 2013; 19 (17): 3033-3042.
- Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 2008; 148 (1): 30-48.
- KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011) 2013; 3 (1): i-150.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a reportof the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Angiotensin II receptor antagonists. Drug Facts and Comparisons [online database]. Wolters Kluwer Health, Inc; 2017. Accessed May 17, 2017.
- Diovan [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.
- AHFS Drug Information. Gerald K. McEvoy PD, ed. 24:32.08 Angiotensin II Receptor Antagonists. 59th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2017.
- Edarbi [package insert]. Atlanta, GA: Arbor Pharmaceuticals, LLC; 2016.
- Atacand [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2016.
- Avapro [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2016.
- Cozaar [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2015.
- Teveten [package insert]. North Chicago, IL: AbbVie Inc.; 2014.
- Micardis [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014.
- Benicar [package insert]. Parsippany, NJ: Daiichi Sankyo, Inc; 2009.
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