The association between albuminuria and long-term renal risk:How to improve the precision of drug effect estimates

Abstract

The worldwide increase in the number of patients with diabetic kidney disease needs to be tackled due to the consequences of the disease. Improving the quality of life and survival of this growing number of patients requires timely access to novel and effective treatments. Timely access to novel treatments can be achieved by decreasing the duration of clinical studies aiming to prove the efficacy of a new drug in preventing dialysis or the requirement of a kidney transplantation. The amount of urinary protein (albuminuria) and its changes are associated with the future risk for dialysis or a kidney transplantation. Changes in albuminuria occur early in the course of the diabetic kidney disease. Hence, using changes in albuminuria levels as a measurement of drug efficacy can decrease the duration of studies in diabetic kidney disease. This thesis examines the use of albuminuria as a measurement of drug efficacy. Part one of this thesis shows that more frequent measurements of albuminuria should be used to monitor the fluctuations in albuminuria levels after treatment initiation. These albuminuria fluctuations need to be taken into account when planning patient treatment aimed at preventing dialysis or the requirement of kidney transplantation. The second part of this thesis describes an optimized way of using albuminuria measurements in efficacy analysis for improving the precision of clinical trial outcomes. In conclusion, the findings presented in this thesis support the use of albuminuria as a measurement of drug efficacy in diabetic kidney disease clinical trials