J Clin Med. 2026 Jul 9;15(14):5359. doi: 10.3390/jcm15145359.
ABSTRACT
Background: Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease and kidney failure worldwide. Although most patients with diabetes are diagnosed clinically on the basis of albuminuria, estimated glomerular filtration rate decline, and diabetic retinopathy, clinical parameters alone may not reliably distinguish biopsy-proven diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) or mixed lesions. The role of kidney biopsy in diabetic patients therefore remains selective rather than routine, but its diagnostic and prognostic value is increasingly relevant in precision nephrology. Methods: This narrative review summarizes clinicopathological evidence on kidney biopsy in patients with diabetes, with particular emphasis on the Renal Pathology Society classification of DN, the prognostic significance of glomerular, tubulointerstitial, and vascular lesions, indications for biopsy, and emerging digital and molecular approaches to renal tissue assessment. Results: Histopathological evaluation provides information that cannot be fully captured by routine clinical markers. While glomerular lesions remain central to the classification of DN, tubulointerstitial fibrosis and tubular atrophy are among the strongest predictors of kidney disease progression. Vascular lesions, particularly arteriolar hyalinosis, also carry renal and cardiovascular prognostic significance. Kidney biopsy is especially valuable in patients with atypical clinical features, including rapid decline in kidney function, acute-onset nephrotic-range proteinuria, active urinary sediment, short diabetes duration, absence of diabetic retinopathy, or suspicion of immune-mediated glomerular disease. In these settings, biopsy may identify NDKD or mixed DN/NDKD, with direct therapeutic implications, including the potential use of disease-specific or immunosuppressive treatment. Emerging technologies, including artificial intelligence-assisted digital pathology, spatial transcriptomics, multi-omics profiling, and biomarker-based "virtual biopsy" models, may further refine lesion quantification and risk stratification, although they currently complement rather than replace tissue-based diagnosis. Conclusions: Kidney biopsy remains a clinically important tool in selected patients with diabetes. Beyond confirming DN, it enables the detection of NDKD, improves prognostic stratification, and supports individualized therapeutic decision-making. A selective, indication-driven biopsy strategy should be regarded as an essential component of precision nephrology in DKD, particularly as histopathology becomes increasingly integrated with digital, molecular, and computational approaches.
PMID:42513273 | PMC:PMC13412735 | DOI:10.3390/jcm15145359