Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease.

Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per study visit. A confirmation of the end point or a requirement of a minimal percentage change in albuminuria from baseline seems unnecessary.