Endocrine Abstracts

Introduction

Diabetic nephropathy is the leading cause of end-stage-kidney disease (ESKD). Clinical practice guidelines recommend prescribing renin–angiotensin aldosterone system inhibitors (RAASi) to prevent diabetic nephropathy at any stage. We conducted this extensive meta-analysis to compare the effects of RAASi with placebo and other antihypertensives in adults with diabetes on binary and continuous renal outcomes to provide a comprehensive review of the class effect of RAASi on several subgroups of study participants.

Methods

A systematic search to identify randomized clinical trials of a duration of 12 months or more that recruited more than 50 adults participants with type 1 or 2 diabetes mellitus with any stage of chronic kidney disease and proteinuria was conducted. Electronic searches were conducted with the help of a librarian in MEDLINE, CINAHL, EMBASE, Cochrane library with no language or date restrictions. Studies were screened against the inclusion and exclusion criteria by two reviewers independently.

Results and discussion

In this meta-analysis, evidence was drawn from 26.609 patients with diabetes from 46 studies on the effect of RAASi on binary and continuous renal outcomes. Our analysis shows that RAASi were superior to placebo in reducing the risks of ESKD(OR:0.74; 95% CI: 0.56–0.97) and doubling of SrCr levels(OR:0.71; 95% CI: 0.55–0.91), but not in promoting the regression of albuminuria(OR:3.00; 95% CI: 0.96–9.37). RAAS inhibitors, however, were not superior to other antihypertensives in reducing the risks of these outcomes. RAASi were better than placebo in reducing SrCr (the raw mean difference (RMD) was -13.4umol/l (95% CI: -16.78; -10.01)) and albuminuria levels (standardized mean difference (SMD) –1(95% CI: –1.57; –0.44, I²=96%)). Surprisingly, RAASi reduced GFR levels more than placebo (RMD:-0.82ml/min;95% CI: -5.54; 3.91), yet it was not a statistically significant finding. When compared to active treatments, RAAS inhibitors did not reduce SrCr levels (RMD:0.03 umol/l;95% CI: -6.4; 6.10, I²=76%), caused a reduction of GFR levels (RMD: -1.12 ml/min; 95% CI: –4.51; 2.09, I²=86%), and resulted in modest reduction of albuminuria levels (SMD:-0.55; 95% CI: -0.95;-0.16, I²=90%). Patients with T2DM, macroalbuminuria and longer duration of DM had less risk to develop ESKD in placebo-controlled trials, while longer duration of DM, normal renal function, and hypertension increased the probability to achieve regression of albuminuria in active-controlled trials.

Conclusion

While our findings revealed the non-superiority of RAASi over other antihypertensives and portrayed class effect on several subgroups of study participants, it raised a challenging question on whether RAASi deserve their place as first-line therapy in managing diabetic nephropathy.