Analytical and Clinical Performance of a Novel Immunoassay-Based Test System to Predict Diabetic Kidney Disease.

Background: Diabetes-related chronic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD), requiring costly dialysis or kidney transplantation. Existing standard- of-care tests for DKD have several limitations, and an alternative is Promarker®D, a validated plasma biomarker test system that predicts DKD in adults with diabetes up to 4 years before symptoms develop.

Methods: To enable high-throughput application of PromarkerD, a novel CaptSureTM immunoassay version of the test was developed targeting plasma biomarkers Apolipoprotein A4 (ApoA4) and CD5 antigen-like (CD5L). The analytical performance of the assay was assessed, and clinical samples from 2 independent clinical cohorts (>1700 adults with type 2 diabetes [T2D]) were used for the development and external validation of the DKD predictive test.

Results: The PromarkerD test system combined ApoA4 and CD5L concentrations with clinical factors age and estimated glomerular filtration rate (eGFR) to calculate risk scores (0% to 100%) and classify study participants as either at low, moderate, or high risk for future kidney decline. PromarkerD demonstrated reliable analytical performance and provided a high discriminative capability in adults with T2D (receiver operating characteristic area under the curve [ROC-AUC]: 0.78 to 0.88) to predict 4-year kidney decline, defined as incident DKD (eGFR <60 mL/min/1.73 m2) or eGFR decline ≥40%, with sensitivity of 75.8% to 85.1% at the moderate-risk cutoff and specificity of >92% at the high-risk cutoff across the two cohorts.

Conclusion: The next-generation PromarkerD test system offers a convenient yet highly effective tool for DKD risk assessment. By introducing PromarkerD to standard diabetes care, preventative treatment strategies may be implemented early before permanent kidney function loss occurs.