Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease

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Title: Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease
Authors: Martin, William P.Conroy, ChloeNaicker, Serika al.
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Date: 26-Aug-2021
Online since: 2022-02-03T14:14:05Z
Abstract: Background We investigated the predictive value of 11 serum biomarkers for renal and mortality end points in people with CKD. Methods Adults with CKD (n=139) were enrolled from outpatient clinics between February 2014 and November 2016. Biomarker quantification was performed using two multiplex arrays on a clinical-grade analyzer. Relationships between biomarkers and renal and mortality end points were investigated by random forests and Cox proportional hazards regression. Results The cohort was 56% male. The mean age was 63 years and median (IQR) CKD-EPI eGFR was 33 (24–51) ml/min per BSA. A total of 56 (40%) people developed a composite end point defined as ≥40% decline in eGFR, doubling of serum creatinine, RRT, or death over median (IQR) follow-up of 5.4 (4.7–5.7) years. Prediction of the composite end point was better with random forests trained on serum biomarkers compared with clinical variables (area under the curve of 0.81 versus 0.78). The predictive performance of biomarkers was further enhanced when considered alongside clinical variables (area under the curve of 0.83 versus 0.81 for biomarkers alone). Patients (n=27, 19%) with high soluble TNF receptor-1 (≥3 ng/ml) and neutrophil gelatinase-associated lipocalin (≥156 ng/ml), coupled with low complement 3a des-arginine (<2368 ng/ml), almost universally (96%) developed the composite renal and mortality end point. C-reactive protein (adjusted hazard ratio, 1.4; 95% CI, 1.1 to 1.8), neutrophil gelatinase-associated lipocalin (adjusted hazard ratio, 2.8; 95% CI, 1.3 to 6.1) and complement 3a des-arginine (adjusted hazard ratio, 0.6; 95% CI, 0.4 to 0.96) independently predicted time to the composite end point. Conclusions Outpatients with the triad of high soluble TNF receptor-1 and neutrophil gelatinase-associated lipocalin coupled with low complement 3a des-arginine had high adverse event rates over 5-year follow-up. Incorporation of serum biomarkers alongside clinical variables improved prediction of CKD progression and mortality. Our findings require confirmation in larger, more diverse patient cohorts.
Funding Details: Health Research Board
Wellcome Trust
Type of material: Journal Article
Publisher: American Society of Nephrology
Journal: Kidney360
Volume: 2
Issue: 8
Start page: 1225
End page: 1239
Copyright (published version): 2021 American Society of Nephrology
Keywords: Chronic kidney diseaseBiomarkersC3a-desArgeEnd stage kidney diseaseMachine learningMortalityMultiplex assaysNeutrophil gelatinase-associated lipocalinRenal function decline
DOI: 10.34067/kid.0007552020
Language: en
Status of Item: Peer reviewed
ISSN: 2641-7650
This item is made available under a Creative Commons License:
Appears in Collections:Conway Institute Research Collection
Medicine Research Collection

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