Non-albumin proteinuria as a candidate biomarker of treatment response to finerenone in diabetic kidney disease: a real-world cohort study.

INTRODUCTION: Finerenone reduces albuminuria and improves kidney outcomes in patients with diabetic kidney disease (DKD); however, its association with changes in non-albumin proteinuria (NAP), enriched for tubular injury-related proteins, remains unclear. We evaluated whether finerenone treatment was associated with a reduction in NAP and identified clinical phenotypes associated with a greater NAP response. METHODS: We retrospectively analyzed 477 patients treated with finerenone who had baseline urine albumin-to-creatinine ratio (uACR) and urine protein-to-creatinine ratio (uPCR) measurements from the same urine specimen. Urine non-albumin protein-to-creatinine ratio (uNAPCR) was calculated as uPCR minus uACR. Patients were stratified by baseline proteinuria severity (uPCR < 500 vs ≥ 500 mg/gCr). The primary outcome was the geometric mean percentage change in uNAPCR after 6 months of finerenone treatment, assessed using linear mixed-effects models. Subgroup interaction analyses were performed to assess differential associations and identify factors associated with greater uNAPCR reduction. RESULTS: At baseline, median uPCR, uACR, and uNAPCR were 1140 [580, 2290], 716 [328, 1593], and 410 [223, 700] mg/gCr, respectively. At 6 months, uACR and uNAPCR declined by 30.3% and 17.5%, respectively. Subgroup analyses revealed differential associations: patients with higher baseline proteinuria (uPCR ≥ 500 mg/gCr) showed an 18.8% decline in uNAPCR, whereas those with uPCR < 500 mg/gCr showed a non-significant 1.3% change. Changes in uNAPCR were positively correlated with changes in urine N-acetyl-β-D-glucosaminidase-to-creatinine ratio (uNAGCR) (Spearman's ρ = 0.53; p < 0.001). DISCUSSION: Finerenone treatment was associated with a reduction in NAP, particularly among patients with higher baseline proteinuria, suggesting a possible effect on tubulointerstitial injury-related processes beyond albuminuria reduction. Prospective multicenter studies are needed to validate uNAPCR as a treatment-response biomarker against clinical endpoints.