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Abstract: FR-PO248

Direct Renin-Inhibitors for Preventing the Progression of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Awan, Ahmed A., Baylor college of medicine, Houston, Texas, United States
  • Strippoli, Giovanni F.M., University of Bari, Bari, Italy
  • Navaneethan, Sankar D., Baylor College of Medicine, Sugar Land, Texas, United States

Renin-angiotensin-aldosterone system blockade using angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy is incomplete and may lead to compensatory rise in angiotensin precursors, including renin. Addition of direct renin-inhibitors (DRIs) to ACEI/ARB treatment might potentially slow down the progression of diabetic kidney disease (DKD). In this systematic review, we examined the benefits and harms of DRIs in preventing the onset or progression of DKD.


We searched CENTRAL, MEDLINE, and EMBASE (until Oct 2018) for relevant clinical trials that compared DRIs to placebo or other agents among those with type 1 or type 2 diabetes and kidney disease (defined by presence of UAER > 30 mg/d or urine albumin creatinine ratio (UACR) > 30 mg/g). Two authors independently screened studies for inclusion and extracted data. Following outcomes were included: all-cause and cardiovascular mortality, progression or regression of albuminuria, changes in blood pressure, and adverse events such as hyperkalemia. Treatment effects were summarized as relative risks (RR) or mean difference (MD) and 95% confidence intervals (CI) using random effects models.


Nine clinical trials (n=10,051) were included. Addition of DRI to ACEI/ARB had no effect on all-cause mortality (2 studies, 9151 participants; RR 0.93, 95% CI: 0.4-2.19), cardiovascular mortality or change in GFR (2 studies,638 participants, Mean difference 1.29, 95% CI: -0.44-3.02 ml/min/1.73 m2) compared to ACEI/ARB use alone. Addition of DRIs to ACEI/ARB was associated with reduced progression to macroalbuminuria (RR 0.82, 95% CI:0.72-0.93) and improvement in regression to microalbuminuria (RR 1.19, 95% CI:1.19-1.29) in one study enrolling 8561 participants. Withdrawal due to adverse events or due to any other reason was similar in both groups. Risk of hyperkalemia was increased by the addition of DRIs to ACEI/ARB therapy (2 studies, 9153 participants, RR 1.34, 95% CI: 1.26-1.42).


Current evidence demonstrate that the addition of DRIs to ACEI/ARB therapy in patients with DKD doesn’t reduce cardiovascular or all-cause mortality. However, it might impart kidney benefits by reducing albuminuria at the cost of higher risk of hyperkalemia.