The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease

Author:

Verbeke Francis1ORCID,Siwy Justyna2,Van Biesen Wim1ORCID,Mischak Harald2,Pletinck Anneleen1,Schepers Eva1,Neirynck Nathalie1,Magalhães Pedro2,Pejchinovski Martin2,Pontillo Claudia2,Lichtinghagen Ralf3,Brand Korbinian3,Vlahou Antonia4,De Bacquer Dirk5,Glorieux Griet1ORCID

Affiliation:

1. Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, Ghent, Belgium

2. Mosaiques-diagnostics GmbH, Hannover, Germany

3. Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany

4. Biotechnology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece

5. Department of Public Health and Primary Care, Ghent University, Ghent, Belgium

Abstract

Abstract Background The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1–G5. Methods We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1–G5 followed prospectively for a median of 5.5 years. Primary endpoints were all-cause mortality, CV mortality and the composite of non-fatal and fatal CV events (CVEs). Results In multivariate Cox regression models adjusting for age, sex, prevalent diabetes and CV history, the CKD273 classifier at baseline was significantly associated with total mortality and time to fatal or non-fatal CVE, but not CV mortality. Because of a significant interaction between CKD273 and CV history (P = 0.018) and CKD stages (P = 0.002), a stratified analysis was performed. In the fully adjusted models, CKD273 classifier was a strong and independent predictor of fatal or non-fatal CVE only in the subgroup of patients with CKD Stages G1–G3b and without a history of CV disease. In those patients, the highest tertile of CKD273 was associated with a >10-fold increased risk as compared with the lowest tertile. Conclusions The urinary CKD273 classifier provides additional independent information regarding the CV risk in patients with early CKD stage and a blank CV history. Determination of CKD273 scores on a random urine sample may improve the efficacy of intensified surveillance and preventive strategies by selecting patients who potentially will benefit most from early risk management.

Funder

Research Foundation—Flanders

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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