Abstract

Since 1957, over 70 equations based on creatinine and/or cystatin C levels have been developed to estimate glomerular filtration rate (GFR). However, whether these equations accurately reflect renal function is debated. In this Perspectives article, we discuss >70 studies that compared estimated GFR (eGFR) with measured GFR (mGFR), involving ~40,000 renal transplant recipients and patients with chronic kidney disease (CKD), type 2 diabetes mellitus or polycystic kidney disease. Their results show that eGFR often differed from mGFR by ±30% or more, that eGFR values incorrectly staged CKD in 30–60% of patients, and that eGFR and mGFR gave different rates of GFR decline. Errors were unpredictable, and comparable for equations based on creatinine and/or cystatin C. We argue, therefore, that the persistence of these errors (despite intensive research) suggests that the problem lies with using creatinine and/or cystatin C as markers of renal function, rather than with the mathematical methods used for GFR estimation.

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Acknowledgements

The authors acknowledge research support from the DIABESITY working group of the ERA-EDTA, the IMBRAIN (CIBICAN) project (FP7-RE6-POT-2012-CT2012-31637-IMBRAIN) funded under the 7th Framework Programme (capacities); Instituto de Salud Carlos III (ISCIII) grants PI13/00342 and PI16/01814 to E.P. and A.T., REDINREN RD16/0009 and PI10/02428 grants to E.P. and A.T.; and funding from the IRSIN (Instituto Reina Sofia de Investigacion) and FEDER (both to A.T.). S.L.L. is a research fellow supported by ISCIII grant CM15/00214 for Río Hortega specialized health-care post-training contracts. E.P. is a researcher supported by the ISCIII Ramón y Cajal Programme and Fundación Caja Canarias grant DIAB05. The authors thank F. G. Rinne for preparation of the figures, N. N. Mena for performing the iohexol method in the Laboratory of Renal Function, and M. L. McLean for technical assistance.

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Nature Reviews Nephrology thanks E. Cavalier, L. Dubourg and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Affiliations

  1. Hospital Universitario de Canarias, Tenerife, Spain

    • Esteban Porrini
    • , Sergio Luis-Lima
    • , Alejandro Jiménez
    •  & Armando Torres
  2. University of La Laguna, ITB: Instituto de Tecnologías Biomédicas, Tenerife, Spain

    • Esteban Porrini
    • , Sergio Luis-Lima
    •  & Armando Torres
  3. Nephrology and Dialysis Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

    • Piero Ruggenenti
    •  & Giuseppe Remuzzi
  4. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro di Ricerche Cliniche per le Malattie Rare “Aldo e Cele Daccò”, Ranica, Bergamo, Italy

    • Piero Ruggenenti
    • , Fabiola Carrara
    • , Flavio Gaspari
    •  & Giuseppe Remuzzi
  5. Leiden University Medical Centre, Department of Medicine, Division of Nephrology, Leiden, Netherlands

    • Aiko de Vries
  6. Department of Biochemical and Clinical Sciences ‘L. Sacco’, University of Milan, Milan, Italy

    • Giuseppe Remuzzi

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Contributions

E.P., F.C. and F.G. researched data for the article, made substantial contributions to discussions of its content, wrote the manuscript and reviewed or edited the manuscript before submission. P.R., A.d.V. and G.R. made substantial contributions to discussions of the article content, wrote the manuscript and reviewed or edited the manuscript before submission. S.L.-L. researched data for the article, contributed substantially to discussions of its content, and reviewed or edited the manuscript before submission. A.J. researched data for the article and contributed substantially to discussions of its content. A.T. substantially contributed to discussions of the article content.

Competing interests

The authors declare no competing interests.

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Correspondence to Esteban Porrini.

Supplementary Information

Glossary

Accuracy

The degree of closeness of the determined value (in this case, estimated glomerular filtration rate) to the true value (measured glomerular filtration rate) under prescribed conditions. Accuracy is also sometimes termed trueness.

Bias

The difference between an estimated value (such as estimated glomerular filtration rate) and a true value (measured glomerular filtration rate), which is also termed error. A statistic is biased if it is calculated in such a way that it is systematically different from the parameter being estimated.

Coefficient of variation

The variation obtained when measurements are repeated under the same conditions. A low value indicates that the technique is both accurate and precise.

Precision

The closeness of agreement (that is, the degree of scatter) in a series of determinations (that is, estimated glomerular filtration rate values) obtained from multiple sampling of the same homogenous sample under the prescribed conditions.

Reproducibility

The precision of results compared between two laboratories. Reproducibility also refers to the precision of a particular method when used under the same operating conditions over a short period of time.

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DOI

https://doi.org/10.1038/s41581-018-0080-9