@article{3330bcd6244a4cbbb812e2936ed94358,
title = "Metabolomic profiling to improve glomerular filtration rate estimation: A proof-of-concept study",
abstract = "Background. Estimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates. Methods. We performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR). Untargeted gas chromatography/dual mass spectrometry– and liquid chromatography/dual mass spectrometry–based quantification was followed by the development of targeted assays for 15 metabolites. On the log scale, GFR was estimated from single- and multiple-metabolite panels and compared with eGFR using the Chronic Kidney Disease Epidemiology equations with creatinine and/or cystatin C using established metrics, including the proportion of errors >30% of mGFR (1-P30), before and after bias correction. Results. Of untargeted metabolites in the AASK and MESA, 283 of 780 (36%) and 387 of 1447 (27%), respectively, were significantly correlated (P 0.001) with mGFR. A targeted metabolite panel eGFR developed in the AASK and validated in the MESA was more accurate (1-P30 3.7 and 1.9%, respectively) than eGFRcr [11.2 and 18.5%, respectively (P < 0.001 for both)] and estimating GFR using cystatin C (eGFRcys) [10.6% (P ¼ 0.02) and 9.1% (P < 0.05), respectively] but was not consistently better than eGFR using both creatinine and cystatin C [3.7% (P > 0.05) and 9.1% (P < 0.05), respectively]. A panel excluding creatinine and demographics still performed well [1-P30 6.4% (P ¼ 0.11) and 3.4% (P < 0.001) in the AASK and MESA] versus eGFRcr. Conclusions. Multimetabolite panels can enable accurate GFR estimation. Metabolomic equations, preferably excluding creatinine and demographic characteristics, should be tested for robustness and generalizability as a potential confirmatory test when eGFRcr is unreliable.",
keywords = "Creatinine, Estimating equations, GFR, Kidney function, Metabolomics",
author = "Josef Coresh and Inker, {Lesley A.} and Yingying Sang and Jingsha Chen and Tariq Shafi and Post, {Wendy S.} and Shlipak, {Michael G.} and Lisa Ford and Kelli Goodman and Regis Perichon and Tom Greene and Levey, {Andrew S.}",
note = "Funding Information: The authors thank the other investigators, the staff and participants in the MESA for valuable contributions. A full list of participating MESA investigators and institutions can be found at www.mesa-nhlbi.org. This research was also supported by the National Institutes of Health; contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung and Blood Institute and grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources. Funding Information: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH; grant R01DK087961). This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research, which is funded in part by grant UL1 TR 001079 from the National Center for Advancing Translational Sciences, a component of the NIH, and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins Institute for Clinical and Translational Research, National Center for Advancing Translational Sciences or the NIH. The funders of this study had no role in the study design; collection, analysis, and interpretation of the data; writing of the report or the decision to submit the report for publication. Funding Information: Provisional patent: Coresh, Inker and Levey filed 8/15/2014 ? ?Precise estimation of GFR from multiple biomarkers? (PCT/US2015/044567). Tufts Medical Center, John Hopkins University and Metabolon have a collaboration agreement to develop a product to estimate GFR from a panel of markers. R.P., L.F. and K.G. are employees of Metabolon and as such have affiliations with or financial involvement with Metabolon. Metabolon owns issued and pending patents in the USA and foreign countries, including those based on PCT/US2014/037762, ?Biomarkers Related to Kidney Function and Methods Using the Same.? Priority date: 14 May 2013. The results presented in this article have not been published previously in whole or part except in abstract format. Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.",
year = "2019",
month = may,
day = "1",
doi = "10.1093/ndt/gfy094",
language = "English (US)",
volume = "34",
pages = "825--833",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "5",
}