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Abstract: FR-PO235

Efficacy and Safety of Endothelin Receptor Antagonist on Renal Outcomes

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Wong, Muh Geot, The George Institute for Global Health , Newtown, New South Wales, Australia
  • Chung, Edmund, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  • Badve, Sunil V., St George Hospital, Kogarah, New South Wales, Australia
  • Jardine, Meg J., The George Institute for Global Health , Newtown, New South Wales, Australia
  • Neuen, Brendon Lange, The George Institute for Global Health , Newtown, New South Wales, Australia
  • Jun, Min, The George Institute for Global Health , Newtown, New South Wales, Australia
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands
  • McMurray, John, University of Glasgow, Glasgow, United Kingdom
  • Perkovic, Vlado, The George Institute for Global Health , Newtown, New South Wales, Australia
Background

Preclinical studies suggest that blockade of the endothelin receptor reduces proteinuria and may confer renal protection. The aim of this systematic review and meta-analysis was to summarize evidence from randomized controlled trials (RCT) concerning the benefits and risks of ERA on renal outcomes.

Methods

MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched for RCTs evaluating ERAs in adults that reported renal outcomes. The primary outcome was kidney failure (end-stage kidney disease, renal failure, or doubling of creatinine, or as reported by the authors). The secondary outcomes were change in kidney function (estimated glomerular filtration rate or creatinine clearance), albuminuria and systolic blood pressure from baseline to last measurement, all-cause mortality, cardiovascular mortality and adverse events. Treatment effects were summarized using random-effects meta-analysis.

Results

Six RCTs (3963 participants, median sample size 333, median follow-up 15 weeks) met eligibility criteria. There was substantial heterogeneity in baseline kidney function and study population. Compared to placebo, ERA significantly reduced the risk of kidney failure (2 trials, risk ratio [RR] 0.75, 95%CI 0.56, 0.93). Compared to placebo, ERA significantly reduced albuminuria (3 trials, SMD -1.19, 95%CI -1.86, -0.53), and systolic blood pressure (weighted mean difference [WMD] -5.86, 95%CI -10.62, -1.09 mm Hg). ERA treatment was associated with a short term decrease in kidney function (5 trials, standardized mean difference [SMD] -0.11, 95%CI -0.22, 0.00). ERA had uncertain effect on all-cause mortality (4 trials, RR 1.62, 95%CI 0.62, 4.29), and pulmonary edema (2 trials, RR 2.07, 95%CI 0.65, 6.59); but increased the risk of systemic edema (6 trials, RR 1.90, 95%CI 1.29, 2.79).

Conclusion

Short-term trials suggest that ERA treatment may reduce the risk of kidney failure and reduce albuminuria. Adequately powered RCTs with long-term follow-up are required to evaluate whether ERA treatment improves renal outcomes.