Heerspink H, Bakris G, Correa-Rotter R, et al. - Urinary albumin creatinine ratio (UACR) response failed to be a causal predictor of atrasentan's treatment effect in diabetic patients with chronic kidney disease (stage 2-4) and a UACR of 300 mg/g-5000 mg/g. Likely contribution of aspects of the trial design, day-to-day variability in albuminuria, and potential long-lasting effects of atrasentan, was suggested due to UACR's variable trajectory with placebo.

• Patients receiving maximum tolerated renin angiotensin system inhibition were included in the SONAR trial, to evaluate long-term impacts on kidney outcomes of atrasentan vs placebo.

• Following 6 weeks of 0.75 mg/day atrasentan (enrichment period), they were randomized (based on UACR response during enrichment) to continue atrasentan or transition to placebo.

• UACR response to atrasentan during enrichment was shown to persist during the double-blind treatment phase and was predictive of primary kidney outcome (a composite of sustained serum creatinine doubling or end-stage kidney).

• Early UACR response to atrasentan during enrichment was found to be also related to the primary kidney outcome during placebo.

• Following placebo correction, elimination of predictive effect of early albuminuria changes during atrasentan was evident, resulting in a consistent relative risk reduction for the primary kidney outcome with atrasentan vs placebo, regardless of the initial UACR response.

• Difference between atrasentan and placebo in UACR during double-blind treatment was shown to be also consistent across UACR response strata.