Osteoactivin/GPNMB as a candidate biomarker of diabetic nephropathy in type 2 diabetes: associations with angiogenic and kidney injury biomarkers.

BACKGROUND: Diabetic nephropathy (DN) is a main complication of type 2 diabetes (T2D) and a major cause of chronic kidney disease and end stage renal failure. Early detection remains challenging, which has attracted interest in exploring novel biomarkers. Osteoactivin is a protein involved in inflammation, tissue repair, and metabolic stress, but its role in DN is not yet fully understood. OBJECTIVE: To evaluate circulating osteoactivin as a potential biomarker of DN, and to examine its relationship with renal dysfunction, angiogenic markers, and diagnostic performance. METHODS: This cross-sectional study included 42 non-diabetic controls, 50 patients with T2D, and 67 patients with DN. Plasma osteoactivin levels were measured using a customized Luminex multiplex assay. Group differences were analyzed using one-way ANOVA or the Kruskal- Walli's test, with post hoc comparisons performed where appropriate. Spearman's correlation was used to assess associations between osteoactivin and various nephropathy-related biomarkers, including Angiopoietin-1, Angiopoietin-2, ANGPTL3, ANGPTL4, ANGPTL6 and ANGPTL8. Multinomial logistic regression was used to examine associations with disease groups. Receiver operating characteristic (ROC) curve analysis was performed to assess diagnostic performance. RESULTS: Circulating osteoactivin levels increased progressively from controls to T2D and were highest in DN (P < 0.001). Higher osteoactivin levels were associated with worse kidney function and showed positive associations with selected angiogenic markers, particularly Angiopoietin-2 (r = 0.414, P < 0.001), ANGPTL4 (r = 0.406, P < 0.001), and ANGPTL8 (r = 0.165, P = 0.039). ROC analysis showed that osteoactivin alone had moderate diagnostic performance (AUC = 0.786), but this improved substantially when combined with angiogenic markers, especially ANGPTL8 (AUC = 0.881), supporting the added value of a multi-marker approach. CONCLUSION: Circulating osteoactivin is associated with renal dysfunction and angiogenic activity in DN and demonstrated moderate diagnostic performance. This was further enhanced when combined with other angiogenic biomarkers, particularly ANGPTL8. These findings support its potential as a non-invasive biomarker tool for the detection and assessment of disease severity in DN.