Performance and Determinants of Serum Creatinine and Cystatin C–Based GFR Estimating Equations in South Asians

Yeli Wang, Andrew S. Levey, Lesley A. Inker, Saleem Jessani, Rasool Bux, Zainab Samad, Ali Raza Khan, Amy B. Karger, John C. Allen, Tazeen H. Jafar

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C-based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown.

Methods: We assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m 2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations.

Results: We found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m 2 [95% confidence interval {CI} 10.7-15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision ( P = 0.52), accuracy ( P = 0.58), or RMSE ( P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%-13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87-0.96] vs. 0.90 [95% CI 0.86-0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass.

Conclusion: eGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.

Original languageEnglish (US)
Pages (from-to)962-975
Number of pages14
JournalKidney International Reports
Volume6
Issue number4
DOIs
StatePublished - Apr 2021

Bibliographical note

Funding Information:
Supported by a research award (1R03TW007588-01A1) from the National Institutes of Health , Fogarty International Center (principal investigator, THJ). The measurements and analyses were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK097020 “Estimating GFR from a Panel of Endogenous Filtration Markers” to Tufts Medical Center. The design, conduct, analysis, interpretation, and presentation of the data were the responsibility of the authors with no involvement from the funder. We thank all research staff for their assistance and acknowledge the cooperation of Ibrahim Mustafa at the Aga Khan University Hospital for logistical assistance with the GFR clinic for research participants and Lise Thibaudin for inulin assays at Renal Laboratories, Saint-Etienne Hospital, University of Jean Monnet, Saint-Etienne, France. We also thank Syed Mansoor Ahmed Shah from Aga Khan University Hospital and Aasim Ahmad and Kiran Nasir from the Kidney Center, Karachi, for referring patients to the study.

Funding Information:
Supported by a research award (1R03TW007588-01A1) from the National Institutes of Health, Fogarty International Center (principal investigator, THJ). The measurements and analyses were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK097020 ?Estimating GFR from a Panel of Endogenous Filtration Markers? to Tufts Medical Center. The design, conduct, analysis, interpretation, and presentation of the data were the responsibility of the authors with no involvement from the funder. We thank all research staff for their assistance and acknowledge the cooperation of Ibrahim Mustafa at the Aga Khan University Hospital for logistical assistance with the GFR clinic for research participants and Lise Thibaudin for inulin assays at Renal Laboratories, Saint-Etienne Hospital, University of Jean Monnet, Saint-Etienne, France. We also thank Syed Mansoor Ahmed Shah from Aga Khan University Hospital and Aasim Ahmad and Kiran Nasir from the Kidney Center, Karachi, for referring patients to the study. THJ, ASL, and LAI were responsible for the research idea and study design. THJ and SJ performed data acquisition. YW, JA, and THJ were responsible for data analysis. YW and THJ were responsible for the interpretation and first draft. All authors submitted critical revisions and were responsible for approval of the final submission. Data are available on reasonable request from THJ subject to approval by the institutional review board.

Publisher Copyright:
© 2021 International Society of Nephrology

Keywords

  • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
  • South Asian
  • cystatin C
  • estimating equations
  • glomerular filtration rate (GFR)
  • kidney function

PubMed: MeSH publication types

  • Journal Article

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