Background: The impact of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on renal outcomes in patients with type 2 diabetes (T2D) and proteinuria remains unclear.

Methods: A search of Medline, Embase and the Cochrane Databases through 11/2/2018 was performed. We included randomized controlled trials (RCTs) of T2D patients and micro- or macroalbuminuria; comparing an ACEI or ARB with placebo, placebo+background antihypertensives or non-ACEI or ARB containing antihypertensives; randomizing ≥100 subjects; and following subjects for ≥12 months. Endpoints included doubling of serum creatinine (SCr), end-stage renal disease (ESRD), all-cause and cardiovascular (CV) mortality and progression and regression of proteinuria. A Hartung-Knapp random-effects model producing a risk ratio (RR) with 95% confidence interval (CI) was employed, with between-study variance calculated using the Paule-Mandel estimator.

Results: The use of an ACE inhibitor or ARB was not associated with a significant reduction in the risk of a doubling in SCr (n=7 trials, RR=0.77, 95% CI=0.50-1.21). ACE inhibitors or ARBs reduced the risk of progressing to ESRD (n=8, RR=0.79, 95CI=0.75-0.83). No difference in all-cause (n=11, RR=0.98, 95% CI=0.89-1.08) or CV mortality (n=6 trials, RR=1.08, 95% CI=0.92-1.28), nor the composite outcome of doubling SCr, development of ESRD or mortality (n=3 trials, RR=0.87, 95% CI=0.72-1.06) were observed. The risk of progression of patients’ proteinuria was decreased when an ACE inhibitor or ARB was used versus control (n=10, RR=0.49, 95% CI=0.33-0.74). The chance of regression of patients’ proteinuria was not significantly improved with an ACE inhibitor or ARB (n=11, RR=1.55, 95% CI=0.93-2.58).

Conclusion: ACEIs and ARBs may reduce the risk of ESRD and slow progression of nephropathy, but do not appear to decrease all-cause or CV mortality in T2D patients with proteinuria.

Disclosure

C.I. Coleman: Research Support; Self; Janssen Scientific Affairs, LLC. E.R. Weeda: None. A.A. Kharat: Consultant; Self; Janssen Scientific Affairs, LLC. B. Bookhart: Employee; Self; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Self; Janssen Pharmaceuticals, Inc. W.L. Baker: None.

Funding

Janssen Scientific Affairs, LLC

© 2019 by the American Diabetes Association.
2019
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.