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

Nienke M. A. Idzerda, Sok Cin Tye, Dick de Zeeuw, Hiddo J. L. Heerspink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.


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.


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].


A drug response score such as the PRE score may assist in improving clinical decision making and implement precision medicine strategies.

Original languageEnglish
Article number2042018820974191
Pages (from-to)2042018820974191
Number of pages7
JournalTherapeutic advances in endocrinology and metabolism
Publication statusPublished - Feb-2021


  • diabetic kidney disease
  • drug response
  • prediction models
  • risk factors

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