Urinary proteomics for prediction of mortality in patients with type 2 diabetes and microalbuminuria

Currie, G. E. et al. (2018) Urinary proteomics for prediction of mortality in patients with type 2 diabetes and microalbuminuria. Cardiovascular Diabetology, 17, 50. (doi:10.1186/s12933-018-0697-9) (PMID:29625564)

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Abstract

Background: The urinary proteomic classifier CKD273 has shown promise for prediction of progressive diabetic nephropathy (DN). Whether it is also a determinant of mortality and cardiovascular disease in patients with microalbuminuria (MA) is unknown. Methods: Urine samples were obtained from 155 patients with type 2 diabetes and confirmed microalbuminuria. Proteomic analysis was undertaken using capillary electrophoresis coupled to mass spectrometry to determine the CKD273 classifier score. A previously defined CKD273 threshold of 0.343 for identification of DN was used to categorise the cohort in Kaplan–Meier and Cox regression models with all-cause mortality as the primary endpoint. Outcomes were traced through national health registers after 6 years. Results: CKD273 correlated with urine albumin excretion rate (UAER) (r = 0.481, p = <0.001), age (r = 0.238, p = 0.003), coronary artery calcium (CAC) score (r = 0.236, p = 0.003), N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.190, p = 0.018) and estimated glomerular filtration rate (eGFR) (r = 0.265, p = 0.001). On multivariate analysis only UAER (β = 0.402, p < 0.001) and eGFR (β = − 0.184, p = 0.039) were statistically significant determinants of CKD273. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p = 0.004), and retained significance (p = 0.048) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. Conclusion: A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the urinary proteomic classifier CKD273 is associated with mortality in individuals with type 2 diabetes and MA even when adjusted for other established cardiovascular and renal biomarkers.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mullen, Dr William and Delles, Professor Christian and Currie, Dr Gemma and Mischak, Professor Harald
Authors: Currie, G. E., von Scholten, B. J., Mary, S., Flores Guerrero, J.-L., Lindhardt, M., Reinhard, H., Jacobsen, P. K., Mullen, W., Parving, H.-H., Mischak, H., Rossing, P., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Cardiovascular Diabetology
Publisher:BioMed Central
ISSN:1475-2840
ISSN (Online):1475-2840
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Cardiovascular Diabetology 17:50
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
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES