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Zacharias, H.U. ; Altenbuchinger, M.* ; Schultheiss, U.T.* ; Samol, C.* ; Kotsis, F.* ; Poguntke, I.* ; Sekula, P.* ; Krumsiek, J. ; Köttgen, A.* ; Spang, R.* ; Oefner, P.J.* ; Gronwald, W.*

A novel metabolic signature to predict the requirement of dialysis or renal transplantation in patients with chronic kidney disease.

J. Proteome Res. 18, 1796–1805 (2019)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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