- Atrasentan reduced the risk of renal events in patients with type 2 diabetes (T2D) and chronic kidney disease.
- In patients with T2D at high risk of end-stage renal disease, selective endothelin receptor antagonists may protect renal function.
Why this matters
- Treatment with a low-dose endothelin A receptor antagonist in T2D reduces albuminuria without causing sodium retention, but long treatment effects on renal outcomes are unknown.
- Double-blind, randomized, placebo-controlled, multicenter trial of adults with T2D with an estimated glomerular filtration rate (eGFR) of 25-75 mL/minute/1.73 m2 and a urine albumin to creatinine ratio (UACR) of 300-5000 mg/g who had received renin-angiotensin inhibitors for 4 weeks.
- Oral atrasentan 0.75 mg daily was given for enrichment period to assess response.
- Responders (patients with 30% decrease in UACR and no substantial fluid retention) (n=2648) were randomly assigned to receive atrasentan or placebo.
- Primary endpoint was a composite of doubling of serum creatinine for ≥30 days, end-stage kidney disease (eGFR 15 mL/minute/1.73 m2 for 90 days), chronic dialysis for >90 days, kidney transplantation, or death from kidney failure in responders.
- At the median follow-up of 2.2 years, the composite renal endpoint had occurred in 79 (6%) atrasentan patients and 105 (7.9%) placebo patients (HR 0.65; 95% CI, 0.49-0.88; P=.0047).
- Fluid retention and anaemia were observed in atrasentan group; hospital admission for heart failure occurred in both groups (3.5%, n=47 in atrasentan vs 2.6%, n=34 in placebo group) (HR 1.33; 95% CI, 0.85-2.07; P=.208).