Studies have shown the progression of kidney disease may be slowed by angiotensin-converting enzyme (ACE) inhibitors by reducing blood pressure, reducing proteinuria, improving renal blood flow, and improving interglomerular pressure due to the vasodilatory effects of ACE inhibitors.1-4
The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) recommends that an ACE inhibitor or angiotensin receptor blocker (ARB) be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours.5 The guideline also suggests an ACE inhibitor or ARB be used in diabetic adults with CKD and urine albumin excretion 30 to 300 mg/24 hours.
The 2017 American College of Cardiology and American Heart Association hypertension guidelines say that ACEIs are a reasonable antihypertensive treatment for adults with CKD to slow kidney disease progression [Moderate recommendation (Level B-R)].6
A 2015 network meta-analysis of randomized trials examined the effect of antihypertensives on all-cause mortality and end-stage renal disease (ESRD) in adults with diabetic kidney disease.4 It found ACE inhibitor monotherapy significantly reduced progression to ESRD in people with diabetes compared to placebo (odds ratio [OR] 0.71, 95% confidence interval [CI] [0.51 – 1.01]). Combination therapy with ARB and ACE inhibitor 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 1999 double-blind placebo controlled trial of 186 patients with chronic non-diabetic nephropathy and persistent proteinuria found that progression to ESRD was significantly less in the ramipril group than placebo group (9/99 vs 18/87, risk ratio [RR] 2.72, 95% CI [1.22 – 6.08]).3 Progression to overt proteinuria was also less in the ramipril group (15/99 vs 27/87, RR 2.40, 95% CI [1.27–4.52]).
A 1996 random controlled trial of 583 patients with renal insufficiency from a variety of underlying diseases including glomerulopathies, interstitial nephritis, and diabetes found that benazepril slowed the progression of renal insufficiency except in patients with polycystic kidney disease.2 Overall unadjusted risk reduction of progressive renal insufficiency was 53% in the benazepril group (71% in those with mild insufficiency and 46% with moderate). The final changes in proteinuria from baseline in the 6-, 12-, 24-, and 36-month cohorts were -31, -40, -30, and -29 percent, respectively, for patients taking benazepril. For those taking a placebo, the final changes from baseline for each cohort were +15, +14, +14, and +9 percent, respectively.
A prospective randomized, double-blind, placebo-controlled trial of captopril on 147 normotensive patients with type 1 diabetes with persistent albumin excretion 20 to 200 mcg/min over 24 months found that 6.0% (4/67) of patients on captopril and 18.6% (13/70) of patients on placebo progressed to clinical proteinuria.1 The albumin excretion rate decreased annually by 17.9% (95% CI [-29.6% – -4.3%]) for people taking captopril, while it increased 11.8% (95% CI [-3.3% – 29.1%]) in the placebo group (p=0.004).
Captopril is FDA-approved for use by people with diabetic nephropathy (proteinuria >500 mg/day) with type 1 diabetes and retinopathy.7 Captopril decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis).
Periodic renal function monitoring is recommended for patients taking ACE inhibitors.7-17 Drugs that inhibit the renin-angiotensin system, such as ACE inhibitors, 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 ACE inhibitor. Doctors should consider withholding or discontinuing treatment in patients who develop a clinically significant decrease in renal function on an ACE inhibitor.
References
- Laffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 1995; 99 (5): 497-504.
- Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996; 334 (15): 939-945.
- Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354 (9176): 359-364.
- 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.
- 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 report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Capoten [package insert]. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2012.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2017.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2017.
- Trandolapril [package insert]. Laurelton, NY: Epic Pharma, LLC; 2017.
- Angiotensin-converting enzyme inhibitors. Drug Facts and Comparisons [online database]. Wolters Kluwer Health, Inc; 2017. Accessed Oct 8, 2017.
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016.
- Moexipril hydrochloride [package insert]. Teva Pharmaceuticals USA Inc; 2016.
- Fosinopril sodium [package insert]. Miami, FL: Ciplo USA Inc; 2015.
- Vasotec [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2014.
- Aceon [package insert]. North Chicago, IL: Abbot Laboratories; 2011.
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