Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, is a promising biomarker of renal functional decline in diabetic kidney disease (DKD). This study aimed primarily to establish normative data and secondarily to evaluate the potential utility of GDF-15 in DKD using Roche Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian population.
Following informed consent, 188 healthy volunteers and 128 participants with diabetes (72 with and 56 without DKD) were recruited to a cross-sectional study. Baseline demographics, anthropometric measurements and laboratory measurements were recorded. Blood for GDF-15 measurement was collected into plain specimen tubes kept at room temperature and processed (centrifugation, separation of serum, freezing at −80 °C) within 1 h of phlebotomy pending batch analyses. Reference intervals were determined using the 2.5th and 97.5th percentiles for serum GDF-15 concentration.
Of 188 healthy participants, 63 failed to meet study inclusion criteria. The reference interval for serum GDF-15 was 399 ng/L (90% confidence interval [CI]: 399–399) – 1335 ng/L (90% CI: 1152–1445). Receiver operator characteristics (ROC) curve analysis for DKD determined the area under the ROC curve to be 0.931 (95% CI: 0.893–0.959; p<0.001). The optimum GDF-15 cutoff for predicting DKD was >1136 ng/L providing a diagnostic sensitivity and specificity of 94.4% and 79%, respectively, and positive likelihood ratio of 4.5:1 (95% CI: 3.4–6.0).
The reference interval for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics ECLIA was established and a preliminary determination of the potential of GDF-15 as a screening test for DKD was made. Further prospective validation with a larger DKD cohort will be required before the cutoff presented here is recommended for clinical use.
We wish to express our gratitude to all volunteers and patients who made this study possible. Special thanks to the scientific, nursing and medical staff at the Centre for Endocrinology, Diabetes and Metabolism, and the Department of Clinical Biochemistry at Saolta University Health Care Group (SUHCG), Galway University Hospitals.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: TPG is supported by a Hardiman Scholarship from the College of Medicine, Nursing and Health Science, National University of Ireland, Galway and a bursary from the Irish Endocrine Society/Royal College of Physicians of Ireland. The authors are supported by grants from the European Commission [Horizon 2020 Collaborative Health Project NEPHSTROM (Funder Id: 10.13039/100010661, grant number 634086; TPG, NI, MDG) and FP7 Collaborative Health Project VISICORT (grant number 602470; MDG)] and from Science Foundation Ireland [REMEDI Strategic Research Cluster (Funder Id: 10.13039/501100001602, grant number 09/SRC-B1794; MDG) and CÚRAM Research Centre (grant number 13/RC/2073; MDG)] and by the European Regional Development Fund. The materials presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0534).
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