A Novel Metabolic Signature To Predict the Requirement of Dialysis or Renal Transplantation in Patients with Chronic Kidney Disease

Journal of Proteome Research
Helena U ZachariasWolfram Gronwald

Abstract

Identification of chronic kidney disease patients at risk of progressing to end-stage renal disease (ESRD) is essential for treatment decision-making and clinical trial design. Here, we explored whether proton nuclear magnetic resonance (NMR) spectroscopy of blood plasma improves the currently best performing kidney failure risk equation, the so-called Tangri score. Our study cohort comprised 4640 participants from the German Chronic Kidney Disease (GCKD) study, of whom 185 (3.99%) progressed over a mean observation time of 3.70 ± 0.88 years to ESRD requiring either dialysis or transplantation. The original four-variable Tangri risk equation yielded a C statistic of 0.863 (95% CI, 0.831-0.900). Upon inclusion of NMR features by state-of-the-art machine learning methods, the C statistic improved to 0.875 (95% CI, 0.850-0.911), thereby outperforming the Tangri score in 94 out of 100 subsampling rounds. Of the 24 NMR features included in the model, creatinine, high-density lipoprotein, valine, acetyl groups of glycoproteins, and Ca2+-EDTA carried the highest weights. In conclusion, proton NMR-based plasma fingerprinting improved markedly the detection of patients at risk of developing ESRD, thus enabling enhanced patient treatment.

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Citations

Sep 11, 2019·Current Opinion in Nephrology and Hypertension·Ibrahim Ali, Philip Kalra
Dec 15, 2020·Biomarker Insights·Ibrahim AliPhilip A Kalra
Jul 24, 2021·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Helena U ZachariasUNKNOWN GCKD Investigators
Aug 7, 2021·Metabolites·Martina HäcklWolfram Gronwald
Aug 7, 2021·Metabolites·Ulla T SchultheissHelena U Zacharias

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