Fractional Excretion of Total Protein and Long‐Term Kidney Outcomes in Patients With Biopsy‐Proven Diabetic Nephropathy: The N‐ BDN Study

Aims Proteinuria is a standard predictor for kidney prognosis in patients with diabetic nephropathy (DN). Even among patients with similar levels of proteinuria, the protein load per functioning nephron can vary substantially depending on the total number of functioning nephrons. We examined whether fractional excretion of total protein (FETP), which reflects the protein load per single functioning nephron, provides superior prognostic value for kidney outcomes compared with conventional proteinuria in DN. Materials and Methods This observational study included patients with biopsy‐proven DN at our institution between June 1981 and December 2014. The primary focus was the incremental prognostic value of adding FETP, compared with proteinuria, to a baseline clinical model for predicting kidney failure requiring replacement therapy (KFRT). Improvements in model discrimination and risk reclassification were quantified using the concordance index (C‐index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results This study included 376 patients with biopsy‐proven DN (median age: 59 years; 62.5% male; median estimated glomerular filtration rate, 58.1 mL/min/1.73 m 2 ). Over a median follow‐up period of 6.7 years, 97 patients developed KFRT. Compared with the proteinuria‐based model, the FETP‐based model showed a significantly higher discrimination ability (ΔC‐index: 0.021 [95% confidence interval (CI): 0.002–0.039]) and improved IDI (0.089 [95% CI: 0.001–0.207]). In contrast, the continuous NRI was not statistically significant. Conclusions FETP was independently associated with KFRT in patients with DN and may provide additional prognostic information beyond conventional proteinuria for risk stratification.