Diagnostic Accuracy and Clinical Determinants of Urinary Podocyte Biomarkers in Paraprotein-Related Kidney Disease

Background: /Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias including MM and MGRS and 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary pro-tein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using Receiver Op-erating Characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p=0.007) and uPCR (p=0.026). Neither podocin nor nephrin mRNA showed sig-nificant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC=0.350) and podocin mRNA (AUC=0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a sig-nificant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs and the pilot na-ture of this study, further research is required to validate these podocyte proteins as prognostic biomarkers in paraprotein-related kidney disease.