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. 2023 Sep 1;18(9):1143-1152.
doi: 10.2215/CJN.0000000000000217. Epub 2023 Jun 20.

Discrepancies between Cystatin C-Based and Creatinine-Based eGFR

Danielle K Farrington  1 , Aditya Surapaneni  2   3 , Kunihiro Matsushita  2 , Jesse C Seegmiller  4 , Josef Coresh  2 , Morgan E Grams  2   3
Affiliations

Discrepancies between Cystatin C-Based and Creatinine-Based eGFR

Danielle K Farrington et al. Clin J Am Soc Nephrol. .

Abstract

Background: Recent guidance suggests clinicians increase use of cystatin C for the estimation of GFR. Discrepant levels of creatinine- versus cystatin C-based eGFR (eGFRcr versus eGFRcys) can occur and might signify inaccurate estimation of GFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy.

Methods: Participants in the Atherosclerosis Risk in Communities Study, a prospective cohort study of US adults, were followed over 25 years. eGFR discrepancy was measured at five clinical visits and defined as eGFRcys either 30% lower or higher than eGFRcr, the current clinical standard of care. The associations between eGFR discrepancies and kidney-related laboratory parameters were assessed using linear and logistic regression and long-term adverse outcomes, including kidney failure, AKI, heart failure, and death, using Cox proportional hazards models.

Results: Among 13,197 individuals (mean age 57 [SD 6] years, 56% women, 25% Black race), 7% had eGFRcys 30% lower than eGFRcr at visit 2 (1990-1992), and this proportion increased over time to 23% by visit 6 (2016-2017). By contrast, the percent with eGFRcys 30% higher than eGFRcr was relatively stable (3%-1%). Independent risk factors for having eGFRcys 30% lower than eGFRcr included older age, female sex, non-Black race, higher eGFRcr, higher body mass index, weight loss, and current smoking. Those with eGFRcys 30% lower than eGFRcr had more anemia and higher uric acid, fibroblast growth factor 23, and phosphate levels as well as higher risk of subsequent mortality, kidney failure, AKI, and heart failure compared with those with similar eGFRcr and eGFRcys values.

Conclusions: Having eGFRcys lower than eGFRcr was associated with worse kidney-related laboratory derangements and a higher risk of adverse health outcomes.

Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000217.mp3.

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Conflict of interest statement

J. Coresh reports ownership interest in Healthy.io; consultancy for Healthy.io and SomaLogic; research funding from National Institute of Health and National Kidney Foundation; and an advisory or leadership role for SomaLogic. D.K. Farrington reports employment with Kidney Care Bermuda and Bermuda Home Dialysis Services Ltd. and MedStar Emergency Medicine Physicians. M.E. Grams reports advisory or leadership roles for ASN Publication Committee, JASN Editorial Fellowship Committee, KDIGO Executive Committee (co-chair elect), NKF Scientific Advisory Board, and USRDS Scientific Advisory Board; role on the Editorial Boards of American Journal of Kidney Diseases and CJASN; grant funding from NKF, which receives funding from multiple pharmaceutical companies; grant funding from NIH; payment from academic institutions for grand rounds; payment from NephSAP; and travel reimbursement from KDIGO and the Korean Society of Nephrology. K. Matsushita reports consultancy for Akebia and Kyowa Hakko Kirin; honoraria from Fukuda Denshi and Kowa Company Ltd.; and advisory or leadership roles for American Journal of Kidney Disease, Circulation Reports, and Kidney International. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Nomogram illustrating the probability of having eGFRcys >30% lower than eGFRcr on the basis of the presence or absence of significant risk factors. BMI, body mass index; eGFRcr, eGFR based on creatinine; eGFRcys, eGFR based on cystatin C; CVD, cardiovascular disease. Figure 1 can be viewed in color in online at www.cjasn.org.
Figure 2
Figure 2
Sankey diagram showing the persistence of having eGFRcys >30% lower than eGFRcr across visits 2–6. Discrepant eGFR refers to having eGFRcys >30% lower than eGFRcr. Figure 2 can be viewed in color in online at www.cjasn.org.
Figure 3
Figure 3
Higher cumulative incidence of adverse outcomes associated with discrepant GFR (eGFRcys >30% lower than eGFRcr), stratified by G categories. (A) Kidney failure, (B) heart failure, (C) AKI, and (D) death. Estimates in A–C account for the competing event of death. G1, CKD stage G1 with eGFRcr ≥ 90 ml/min per 1.73 m2; G2, CKD stage G2 with eGFRcr 60–90 ml/min per 1.73 m2; G3+, CKD stage G3 or higher with eGFRcr <60 ml/min per 1.73 m2.
See this image and copyright information in PMC

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