Kidney Week

Abstract: PO0569

CKD Progression End Points as Potential Surrogates for Kidney Failure: Findings from the CKDopps

Session Information

• CKD Clinical, Outcomes, and Trials - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Zee, Jarcy, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Jarcy Zee,

• Muenz, Daniel G., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Daniel G. Muenz,

• McCullough, Keith, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Keith McCullough,

• Bieber, Brian, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Brian Bieber,

• Metzger, Marie, French Institute of Health and Medical Research (INSERM), Villejuif, France

Marie Metzger,

• Alencar de Pinho, Natalia, French Institute of Health and Medical Research (INSERM), Villejuif, France

Natalia Alencar de Pinho,

• Lopes, Antonio Alberto, Department of Internal Medicine, Federal University of Bahia, Salvador, Brazil

Antonio Alberto Lopes,

• Fliser, Danilo, Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes, Homburg, Saarland, Germany

Danilo Fliser,

• Robinson, Bruce M., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Bruce M. Robinson,

• Young, Eric W., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Eric W. Young,

• Pisoni, Ronald L., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Ronald L. Pisoni,

• Stengel, Benedicte, French Institute of Health and Medical Research (INSERM), Villejuif, France

Benedicte Stengel,

• Pecoits-Filho, Roberto, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Roberto Pecoits-Filho,

Background

Many potential surrogate endpoints for kidney failure (KF) have been used in clinical trials and observational studies of chronic kidney disease (CKD). Individual and composite surrogate endpoints must be compared to ensure accurate research that maximizes power and facilitates harmonization across studies, particularly among an international sample of advanced CKD patients.

Methods

Using data from CKD stage 3-5 patients from Brazil, France, Germany, and the US enrolled in the CKD Outcomes and Practice Patterns Study (CKDopps), we defined potential individual surrogate KF endpoints based on reaching (1) eGFR<15 mL/min/1.73m² and (2) eGFR decline of ≥40%, and composite surrogate endpoints that combine (1) and (2) with and without kidney replacement therapy (KRT, dialysis or transplant). We used each individual and composite endpoint as a time-varying indicator in an unadjusted Cox model to predict time from study entry to the hard outcome of KRT. Potential surrogate endpoints were compared by number of events and prediction accuracy (integrated area under the time-varying receiver operating curve [iAUC]).

Results

N=5242 patients had median (IQR) baseline eGFR of 26.8 (20.7-35.5) and 1448 KRT events over a median (IQR) follow-up time of 2.7 (1.2-3.0) years. Potential surrogate endpoints that included eGFR<15 had higher prediction discrimination compared with those that only included 40% eGFR decline (Figure, iAUCs of 0.83-0.84 vs. 0.73-0.73). Composite endpoints had higher event counts than non-composite endpoints (Ns of 1622-1878 vs. 1144-1356, see Figure x-axis).

Conclusion

A composite KF endpoint defined by the earliest occurrence of either KRT, eGFR<15, or eGFR decline of 40% had the highest prediction discrimination for KRT and the highest number of events among a cohort enrolled at low eGFR. This endpoint should be further evaluated and considered for clinical research studies to optimize power while sufficiently capturing KF.