We thank Groothof et al.1 for their letter and the opportunity to clarify certain aspects of our analysis.2 In our calculation of eGFR based on creatinine (eGFRcr), eGFR based on cystatin C (eGFRcys), and eGFRcr-cys, we followed current recommendations for reporting cystatin C (using two decimals for values in mg/L) and for serum creatinine (using two decimals for values in mg/dl and integers for values in micromole/L).3,4 Thus, we did not round cystatin C values to the nearest integer before calculations as asserted by Groothof et al. In our baseline table, we rounded cystatin C to the nearest integer; here, we present them using 2 decimals for the interested reader: 1.28 (0.97 to 1.80) mg/L in the overall population, 1.57 (1.23 to 2.12) mg/L for eGFRcys<eGFRcr, 1.01 (0.85 to 1.37) mg/L for eGFRcys≈eGFRcr, and 0.96 (0.80–1.96) mg/L for eGFRcys>eGFRcr.
We did not implement a stratified bootstrap but performed bootstrapping followed by stratification by discordance group. Reanalysis using a stratified bootstrap leads to virtually identical results: For the eGFRcys>eGFRcr discordance group, median biases (95% confidence interval [CI]) using a stratified bootstrap are −4.5 (−5.3 to −3.8) ml/min per 1.73 m2 for eGFRcr, 8.4 (7.3 to 10.0) for eGFRcys, and 1.8 (1.1 to 2.5) for eGFRcr-cys. For the eGFRcys<eGFRcr discordance group, median biases (95% CI) using a stratified bootstrap are 15.0 (14.5 to 15.5) ml/min per 1.73 m2 for eGFRcr, −8.6 (−9.0 to −8.3) for eGFRcys, and 0.7 (0.5 to 1.0) for eGFRcr-cys.
Similar to Groothof et al., we now also reanalyzed our data by rounding cystatin C values to one decimal or the nearest integer before calculating eGFR. Rounding cystatin C values to one decimal or the nearest integer would result in sample sizes of 736 and 1150, respectively, in the eGFRcys>eGFRcr discordance group (compared with 713 in our main analysis that used two decimals). When rounding cystatin C to one decimal before eGFR calculation, median biases (95% CI) in the eGFRcys>eGFRcr discordance group would be −4.4 (−5.3 to −3.8) ml/min per 1.73 m2 for eGFRcr, 9.5 (7.9 to 11.2) for eGFRcys, and 2.0 (1.5 to 2.8) for eGFRcr-cys. For the eGFRcys<eGFRcr group, median biases would be 15.0 (14.5 to 15.5), −8.7 (−9.0 to −8.3), and 0.7 (0.4 to 1.0), respectively. When rounding cystatin C to the nearest integer, median biases (95% CI) would be −1.0 (−1.3 to −0.5) for eGFRcr, 18.4 (17.4 to 19.3) for eGFRcys, and 10.1 (9.2 to 11.0) for eGFRcr-cys. For the eGFRcys<eGFRcr group, median biases would be 13.1 (12.6 to 13.6), −11.2 (−11.8 to −10.8), and −1.6 (−1.9 to −1.2), respectively.
In conclusion, we agree with Groothof et al. that researchers should use two decimals for cystatin C values in mg/L before calculating eGFR.
Acknowledgments
Research reported in this publication was supported by the Swedish Research Council (2019-01059) and the Dutch Kidney Foundation (22OK2026). ELF is supported by a Rubicon Grant from the Netherlands Organization for Scientific Research (NWO) and an internal funding grant from Karolinska Institute.
Footnotes
See related letter to the editor, “Integer cystatin C values: Impact on discordance group assignment and accuracy of GFR-estimating equations” on pages 1915–1916 and original article, “Accuracy of GFR estimating equations in patients with discordances between creatinine and cystatin C-based estimations,” in Vol. 34, Iss. 7, on pages 1241–1251.
Disclosures
J-J. Carrero reports research funding: Amgen, Astellas, MSD, NovoNordisk, Swedish Heart and Lung Foundation, Swedish Research Council, and ViforPharma; advisory or leadership role—Advisory Committee: AstraZeneca and GSK; Editorial board: Am J Kidney Disease and Eur Heart J, Journal of Nephrology, Nephrology, Dialysis and Transplantation; speakers bureau: Abbott Laboratories, AstraZeneca, Baxter, Fresenius Kabi, and GSK; and other interests or relationships: European Renal Nutrition working group at the ERA-EDTA and Ïnternational Society of Renal Nutrition and Metabolism. L.A. Inker reports consultancy: Diamtrix and Tricia Inc.; research funding: funding to institute for research and contracts with the Chinnocks, National Institutes of Health, National Kidney Foundation, Omeros and Reata Pharmaceuticals; advisory or leadership role: Alport Foundation—Medical Advisory Council, NKF—Scientific Advisory Board; and other interests or relationships: American Society of Nephrology member and National Kidney Foundation member. A.S. Levey reports research funding: grants and contracts paid to Tufts Medical Center: NIH, NKF; contracts paid to me: AstraZeneca (DSMB for dapagliflozin trials); and honoraria: Academic medical centers for visiting professorships. All remaining authors have nothing to disclose.
Funding
This work is supported by Nierstichting from 22OK2026 and ZonMw (E.L. Fu).
Author Contributions
Conceptualization: Edouard L. Fu, Lesley A. Inker, Andrew S. Levey.
Formal analysis: Edouard L. Fu.
Investigation: Andrew S. Levey.
Methodology: Edouard L. Fu.
Project administration: Juan-Jesus Carrero.
Resources: Juan-Jesus Carrero.
Supervision: Juan-Jesus Carrero, Andrew S. Levey.
Writing – original draft: Edouard L. Fu.
Writing – review & editing: Juan-Jesus Carrero, Lesley A. Inker, Andrew S. Levey.
References
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