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Strengths and limitations of estimated and measured GFR

Nature Reviews Nephrology volume 15, page 784 (2019)Cite this article

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Evaluation of glomerular filtration rate (GFR) is central to medical practice, research and public health. As investigators who developed the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for estimation of GFR, and as leaders of national and international guideline committees and workshops on the use of estimated GFR (eGFR), we take issue with the conclusions of Porrini et al. stated in their Perspectives article (Porrini, E. et al. Estimated GFR: time for a critical appraisal. Nat. Rev. Nephrol. 15, 177–190 (2019)1), which discusses the reliability of eGFR equations. These authors conclude that “eGFR is an unreliable tool to assess renal function in health and disease, as well as in clinical practice and research”. Instead of eGFR, they recommend more frequent use of measured GFR (mGFR). We agree that eGFR may be imprecise; using the most accurate eGFR equations, the proportion of eGFR values that are within 30% of mGFR values (P30) generally does not exceed 90%, which is the performance goal for eGFR2,3. We also agree that more frequent use of mGFR is desirable, and we applaud the work of Porrini et al. in implementing plasma clearance of iohexol in research studies. However, we regard their conclusions as flawed for several reasons.

First, their analysis includes studies that did not standardize assays for creatinine or cystatin C, leading to unpredictable bias in eGFR values based on levels of creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr–cys), and to unreliable estimates of the accuracy of these equations. This flaw can only be avoided by limiting the analysis to studies that used standardized assays and equations developed or re-expressed for use with standardized assays4.

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Acknowledgements

We acknowledge the assistance of J. Chaudhari (Tufts Medical Center, Boston, MA, USA) in manuscript preparation.

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Authors and Affiliations

  1. Division of Nephrology, Tufts Medical Center, Boston, MA, USA

    Andrew S. Levey & Lesley A. Inker

  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Josef Coresh

  3. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA

    Hocine Tighiouart

  4. Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Tom Greene

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  1. Andrew S. Levey
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Corresponding author

Correspondence to Andrew S. Levey.

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Competing interests

A.S.L. has received grants from the US National Institutes of Health (NIH) and the National Kidney Foundation (NKF) for research related to eGFR equations. J.C. has received grants from the NIH and the NKF, some of which are related to the development of eGFR equations. T.G. reports grants from the NKF and personal fees from DURECT Corporation, Janssen Pharmaceuticals and Pfizer Inc. L.A.I. reports funding awarded to Tufts Medical Center for research and contracts with the NIH, NKF, Retrophin, Omeros, Reata Pharmaceuticals and Dialysis Clinic, Inc. She also has consulting agreements with Tricida Inc. and Omeros. A.S.L., J.C. and L.A.I. have a patent pending for precise estimation of GFR using multiple biomarkers (filed 15 Aug 2014; patent number PCT/US2015/044567). Tufts Medical Center, John Hopkins University and Metabolon Inc. have a collaboration agreement to develop a product to estimate GFR from a panel of markers. H.T. declares no competing interests.

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Levey, A.S., Coresh, J., Tighiouart, H. et al. Strengths and limitations of estimated and measured GFR. Nat Rev Nephrol 15, 784 (2019). https://doi.org/10.1038/s41581-019-0213-9

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