The kidney failure risk equation: evaluation of novel input variables including eGFR estimated using the CKD-EPI 2021 equation in 59 cohorts

Morgan E. Grams (Lead / Corresponding author), Nigel J. Brunskill, Shoshana H. Ballew, Yingying Sang, Josef Coresh (Lead / Corresponding author), Kunihiro Matsushita, Aditya Surapaneni, Samira Bell, Juan J. Carrero, Gabriel Chodick, Marie Evans, Hiddo J. L. Heerspink, Lesley A. Inker, Kunitoshi Iseki, Philip A. Kalra, H. Lester Kirchner, Brian J. Lee, Adeera Levin, Rupert W. Major, James MedcalfGirish N Nadkarni, David M. J. Naimark, Ana C. Ricardo, Simon Sawhney, Manish M. Sood, Natalie Staplin, Nikita Stempniewicz, Bénédicte Stengel, Keiichi Sumida, Jamie P. Traynor, Jan van den Brand, Chi-Pang Wen, Mark Woodward, Jae Won Yang, Angela Yee-Moon Wang, Navdeep Tangri

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Abstract

Significance StatementThe kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2. However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities.BackgroundThe kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2.MethodsUsing 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death.ResultsThe KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall.ConclusionsThe original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.

Original languageEnglish
Pages (from-to)482-494
Number of pages13
JournalJournal of the American Society of Nephrology
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 2023

Keywords

  • kidney failure
  • risk factors
  • glomerular filtration rate
  • chronic kidney disease
  • albuminuria

ASJC Scopus subject areas

  • General Medicine

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