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Cardiovasc Diabetol. 2018 Apr 6;17(1):50. doi: 10.1186/s12933-018-0697-9.

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

Author information

1
Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK. gemma.currie@glasgow.ac.uk.
2
Steno Diabetes Center, Gentofte, Copenhagen, Denmark.
3
Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
4
Mosaiques Diagnostics, Hanover, Germany.
5
HEALTH, University of Aarhus, Aarhus, Denmark.
6
Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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.

KEYWORDS:

Biomarkers; Diabetes; Microalbuminuria; Mortality; Proteomics

PMID:
29625564
PMCID:
PMC5889591
DOI:
10.1186/s12933-018-0697-9
[Indexed for MEDLINE]
Free PMC Article

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