ArticleFrontiers in endocrinology2026
Non-albumin proteinuria as a candidate biomarker of treatment response to finerenone in diabetic kidney disease: a real-world cohort study.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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