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January 5, 2022

Potential Role and Limitations of Estimated Glomerular Filtration Rate Slope Assessment in Cardiovascular Trials: A Review

Author Affiliations
  • 1Division of Cardiology, Duke University School of Medicine, Durham, North Carolina
  • 2Department of Medicine, University of Chicago Medical Center, Chicago
  • 3Department of Medicine, Ziauddin University, Karachi, Pakistan
  • 4Division of Nephrology, University of Maryland School of Medicine, Baltimore
  • 5Department of Medicine, University of Mississippi Medical Center, Jackson
JAMA Cardiol. 2022;7(5):549-555. doi:10.1001/jamacardio.2021.5151

Importance  Cardiovascular trials have traditionally been underpowered to assess advanced chronic kidney disease (CKD) outcomes, and when included as a secondary end point, trials have used progression of CKD as incidence of some variation of a composite of end-stage kidney disease (ESKD) outcomes. Such outcomes are infrequent or occur late in cardiovascular outcome trials, which highlights the need for alternate markers for assessing the impact of interventions on kidney function at an earlier stage of the disease and, from the prevention perspective, more relevant stage of the disease.

Observations  Estimated glomerular filtration rate (eGFR) slope has demonstrated strong association with subsequent progression to ESKD. With adequate sample size, treatment effects in the range of 0.5 to 1.00 mL/min/1.73 m2/y had 96% probability of predicting CKD progression, defined as doubling of serum creatinine, eGFR less than 15 mL/min/1.73 m2, or ESKD. eGFR slope can be used in patients with higher baseline values and may provide CKD progression insights when few hard kidney events are observed, especially in trials with limited follow-up. However, among trials that have determined eGFR slope, significant variations exist regarding inclusion of baseline values, calculation of eGFR values, and the follow-up period, which make it difficult to compare and gauge the incremental benefit of the interventions. There are multiple challenges in computing eGFR slope in cardiovascular trials, such as accounting for initial eGFR dip, nonlinearity, and heteroscedasticity.

Conclusions and Relevance  eGFR slope may serve as a valuable marker to determine progression of CKD in cardiovascular trials. Further work is required to standardize data collection, follow-up duration, time points for kidney function assessment, and analytic methods to compute eGFR slope in cardiovascular trials.

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