Prediction of chronic kidney disease stage 3 by CKD273, a urinary proteomic biomarker

Pontillo, C. et al. (2017) Prediction of chronic kidney disease stage 3 by CKD273, a urinary proteomic biomarker. Kidney International Reports, 2(6), pp. 1066-1075. (doi: 10.1016/j.ekir.2017.06.004) (PMID:29130072) (PMCID:PMC5669285)

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Introduction: CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m2. Methods: In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m2, 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers. Results: Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m2; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m2), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086). Discussion: In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.

Item Type:Articles
Keywords:Biomarker, chronic kidney disease, clinical science, glomerular filtration rate, peptidomics, proteomics.
Glasgow Author(s) Enlighten ID:Mullen, Dr Bill and Delles, Professor Christian and Mischak, Professor Harald
Authors: Pontillo, C., Zhang, Z.-Y., Schanstra, J. P., Jacobs, L., Zürbig, P., Thijs, L., Ramírez-Torres, A., Heerspink, H. J.L., Lindhardt, M., Klein, R., Orchard, T., Porta, M., Bilous, R. W., Charturvedi, N., Rossing, P., Vlahou, A., Schepers, E., Glorieux, G., Mullen, W., Delles, C., Verhamme, P., Vanholder, R., Staessen, J. A., Mischak, H., and Jankowski, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Kidney International Reports
Published Online:15 June 2017
Copyright Holders:Copyright © 2017 International Society of Nephrology
First Published:First published in Kidney International Reports 2(6): 1066-1075
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
573932PRIORITY: Intervention study for the prevention of diabetic nephropathyChristian DellesEuropean Commission (EC)279277RI CARDIOVASCULAR & MEDICAL SCIENCES
601881HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507RI CARDIOVASCULAR & MEDICAL SCIENCES
637441IMODE-CKD: Clinical and system-omics for the identification of the Molecular Determinants of established Chronic Kidney DiseaseHolger HusiEuropean Commission (EC)608332RI CARDIOVASCULAR & MEDICAL SCIENCES