Defining reference intervals for a serum growth differentiation factor-15 (GDF-15) assay in a Caucasian population and its potential utility in diabetic kidney disease (DKD).

Background: 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. Methods: 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 scrum, freezing at -80 degrees 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. Results: 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]: 399399) - 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). Conclusions: 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.