A novel drug response score more accurately predicts renoprotective drug effects than existing renal risk scores

Abstract

Background: Risk factor-based equations are used to predict risk of kidney disease progression in patients with type 2 diabetes order to guide treatment decisions. It is, however, unknown whether these models can also be used to predict the effects of drugs on clinical outcomes. Methods: The previously developed Parameter Response Efficacy (PRE) score, which integrates multiple short-term drug effects, was first compared with the existing risk scores, Kidney Failure Risk Equation (KFRE) and The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) renal risk score, in its performance to predict end-stage renal disease (ESRD; KFRE) and doubling of serum creatinine or ESRD (ADVANCE). Second, changes in the risk scores were compared after 6 months’ treatment to predict the long-term effects of losartan on these renal outcomes in patients with type 2 diabetes and chronic kidney disease. Results: The KFRE, ADVANCE and PRE scores showed similarly good performance in predicting renal risk. However, for prediction of the effect of losartan, the KFRE risk score predicted a relative risk change in the occurrence of ESRD of 3.1% [95% confidence interval (CI) −5 to 12], whereas the observed risk change was −28.8% (95% CI −42.0 to −11.5). For the composite endpoint of doubling of serum creatinine or ESRD, the ADVANCE score predicted a risk change of −12.4% (95% CI −17 to −7), which underestimated the observed risk change −21.8% (95% CI −34 to −6). The PRE score predicted renal risk changes that were close to the observed risk changes with losartan treatment [−24.0% (95% CI −30 to −17) and −22.6% (95% CI −23 to −16) for ESRD and the composite renal outcome, respectively]. Conclusion: A drug response score such as the PRE score may assist in improving clinical decision making and implement precision medicine strategies.