Repurposing a prostate tumor marker: elevated FPSA/TPSA ratio as a novel non-invasive biomarker for declining eGFR in male type 2 diabetes

Background Diabetic kidney disease (DKD) lacks accessible, cost-effective biomarkers for early screening. Given the distinct clearance pathways of free prostate-specific antigen (FPSA, renally excreted) and total prostate-specific antigen (TPSA, hepatically metabolized), this study investigated the association between serum FPSA/TPSA ratio and estimated glomerular filtration rate (eGFR) in male patients with type 2 diabetes mellitus (T2DM). Methods In this real-world cross-sectional study, 4,487 male patients with T2DM were retrospectively enrolled. eGFR was determined using the Kidney Disease: Improving Global Outcomes (KDIGO)-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C (Cr-CysC) equation. Multivariable linear regression and subgroup analyses were conducted to elucidate the independent effect of the FPSA/TPSA ratio on eGFR, with adjustment for age, prostate-specific diseases, and metabolic confounders. Results Baseline TPSA levels remained stable across renal function stages (median 0.9ng/ml, P = 0.524), minimizing interference from macroscopic prostate pathologies. After adjustment for age and metabolic profiles, the FPSA/TPSA ratio exhibited a robust independent negative association with eGFR (β = −0.2, P < 0.001). This inverse correlation remained consistent across all clinical subgroups (P for interaction > 0.05), with a more pronounced predictive trend among elderly patients (≥ 65 years). Notably, our multivariable models also captured the chronic kidney disease “lipid paradox”, whereby higher triglyceride levels paradoxically correlated with preserved eGFR (β = 0.51, P = 0.018). Conclusion An elevated serum FPSA/TPSA ratio is a robust, non-invasive indicator of declining eGFR in male patients with T2DM and may improve DKD risk stratification and early clinical warning without additional economic burden.