Clinical significance of renal histological diagnosis in patients with type 2 diabetes and proteinuria atypical for diabetic nephropathy

ABSTRACT Background/Aim Most patients with proteinuria are considered to have typical diabetic nephropathy (DN). However, when proteinuria occurs without diabetic retinopathy, with hematuria, or persists despite strict glycemic and blood pressure control, it is considered atypical for DN and warrants further evaluation for non‐DN via kidney biopsy. Nevertheless, comprehensive information on renal histopathology and prognosis following kidney biopsy remains limited. This study aimed to clarify these issues through a retrospective analysis. Methods Among 490 patients who underwent kidney biopsy at Shiga University of Medical Science Hospital between 2013 and 2024, 51 Japanese patients with type 2 diabetes who met at least one criterion for proteinuria atypical for DN were included. Pre‐ and post‐biopsy changes in proteinuria levels and eGFR decline rate, as well as renal histology, were analyzed. Results Among the 51 patients, 17 (33.3%) were histologically diagnosed with typical DN, whereas 34 (66.7%) were diagnosed with non‐DN, including membranous nephropathy, immunoglobulin A (IgA) nephropathy, renal sclerosis, interstitial nephritis, vasculitis, and others. Compared with the DN group, patients with non‐DN were significantly older and had a lower prevalence of diabetic retinopathy. Additionally, the non‐DN group showed significant improvements in both proteinuria levels and in the eGFR decline following biopsy and appropriate disease‐specific therapy. Conclusion A kidney biopsy identified a wide range of kidney diseases as the underlying causes of atypical proteinuria in DN, particularly in elderly patients, thereby improving renal outcomes. These findings underscore the clinical importance of heightened awareness of atypical proteinuria in diabetes management, particularly in aging populations.