Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes

Kammer, M. et al. (2018) Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes. Diabetes Care, 41(9), pp. 1947-1954. (doi: 10.2337/dc18-0532) (PMID:29980527) (PMCID:PMC6105325)

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Objective: The decline of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes is variable and early interventions would likely be cost effective. We elucidated the contribution of 17 plasma biomarkers to the prediction of eGFR loss on top of clinical risk factors. Research Design and Methods: We studied participants in PROVALID, a prospective multinational cohort study of patients with type 2 diabetes and a follow up of more than 24 months (n = 2560; baseline median eGFR 84 mL/min/1.73m2, UACR 8.1 mg/g). The 17 biomarkers were measured at baseline in 481 samples using Luminex technology and ELISA. The prediction of eGFR decline was evaluated by linear mixed modeling. Results: In univariable analyses nine of the 17 markers showed significant differences in median concentration between the two groups. A linear mixed model for eGFR obtained by variable selection exhibited an adjusted R2 of 62%. A panel of twelve biomarkers was selected by the procedure and accounted for 34% of the total explained variability, of which 32% were due to five markers. Each biomarker’s individual contribution to the prediction of eGFR decline on top of clinical predictors was generally low. When included into the model, baseline eGFR exhibited the largest explained variability of eGFR decline (R2 of 79%) and the contribution of each biomarker dropped below 1%. Conclusions: In this longitudinal study of patients with type 2 diabetes and maintained eGFR at baseline, 12 of the 17 candidate biomarkers were associated with eGFR decline, but their predictive power was low.

Item Type:Articles
Additional Information:This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. MMcC is a Wellcome Senior Investigator supported by Wellcome grants 090532 098381 and 203141. This work was partially supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (P30DK081943, to M.Kr.). This work was also supported by JDRF award 2-SRA-2014-276-Q-R, and by IMI funding to the SUMMIT consortium.
Glasgow Author(s) Enlighten ID:Mark, Dr Patrick
Authors: Kammer, M., Heinzel, A., Mayer, G., Reindl-Schwaighofer, R., Hu, K., Perco, P., Eder, S., Rosivall, L., Mark, P. B., Ju, W., Kretzler, M., Gilmour, P., Wilson, J. M., Duffin, K. L., Abdalla, M., McCarthy, M. I., Heerspink, H. L., Wiecek, A., Gomez, M. F., and Oberbauer, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetes Care
Publisher:American Diabetes Association
ISSN (Online):1935-5548
Published Online:06 July 2018
Copyright Holders:Copyright © 2018 American Diabetes Association
First Published:First published in Diabetes Care 41(9): 1947-1954
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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