Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria

Aim To assess the impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria. Methods A literature search up to 6 June 2019 was performed. We included randomized trials of >= 100 participants with Type 2 diabetes and micro- or macroalbuminuria comparing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with placebo +/- background anti-hypertensives or non-angiotensin-converting enzyme inhibitor or angiotensin receptor blocker-containing anti-hypertensives, which included follow-up of >= 12 months. Endpoints included doubling of serum creatinine, end-stage renal disease, all-cause and cardiovascular mortality and progression and regression of proteinuria. A Hartung-Knapp random-effects model (between-study variance calculated using the Paule-Mandel estimator) producing a risk ratio with 95% confidence interval was employed. Results The use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was not associated with a significant reduction in the risk of a doubling in serum creatinine (n = 7 trials, RR = 0.77, 95% CI = 0.50-1.21). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers reduced the risk of progressing to end-stage renal disease (n = 8, RR = 0.79, 95% CI = 0.75-0.83). No difference in all-cause (n = 11, RR = 0.98, 95% CI = 0.89-1.08) or cardiovascular mortality (n = 6 trials, RR = 1.08, 95% CI = 0.92-1.28), nor the composite outcome of doubling in serum creatinine, end-stage renal disease or mortality (n = 3 trials, RR = 0.87, 95% CI = 0.72-1.06), was observed. Progression of proteinuria was decreased with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use vs. control (n = 10, RR = 0.49, 95% CI = 0.33-0.74). Regression of proteinuria was not improved with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (n = 11, RR = 1.55, 95% CI = 0.93-2.58). Conclusion Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce the risk of end-stage renal disease and slow the progression of nephropathy, but they do not appear to decrease all-cause or cardiovascular mortality in people with Type 2 diabetes and proteinuria.