Combining UACR and GFR improves prediction of drug effect in CKD phase 2 trials

A new strategy that combines change in urinary albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) slope – markers that are used individually as surrogates of chronic kidney disease (CKD) progression in clinical trials – improves the prediction of drug effects on clinical outcome in phase 2 trials [1].

Although UACR change and GFR slope are both used in phase 2 studies, integrating their information has not been straightforward, until now. By using data from 41 randomised controlled trials of CKD progression and subsequently using UACR change and GFR slope, individually or in combination, researchers were able to demonstrate that combining UACR change and GFR slope improves predictions of treatment effects on clinical endpoints, including mortality and end-stage kidney disease, defined as renal replacement therapy or an eGFR of <15 mL/min/1.73 m². Dr Tom Greene (University of Utah, USA) explained the idea behind this combination: “We used a Bayesian model to characterise the relationships among the treatment effects on UACR, GFR slope, and the clinical endpoint across previous randomised trials. In the second step, this model was used to provide a unified estimate of the probability of clinical benefit based on the estimated effects of the treatment on UACR change and GFR slope in a new phase 2 trial.”

1. Greene T, et al. Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Trials. SA-OR38, ASN Kidney Week 2022, 3–6 Nov.

 

 

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Posted on 8 December 202217 May 2024