Class IV Lesions Dominate 50.4 Percent of Diabetic Nephropathy Biopsies, Suggests Study
A recent retrospective study published in the Indian Journal of Pathology and Oncology in September 2026 revealed that advanced Class IV lesions accounted for a striking 50.4% of diabetic nephropathy biopsies. Higher histopathological grades strongly correlated with severe renal decline, characterized by an average serum creatinine of 5.53 mg/dL and heavy proteinuria of 5.69 g/day.
With diabetes mellitus affecting 11.4% of adults in India per the Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study and up to 40% developing renal impairment, differentiating pure DN from Non-Diabetic Renal Disease (NDRD) remains clinically challenging due to atypical presentations. Addressing this diagnostic gap, Dr. Vinay K. S. and colleagues from the Departments of Pathology and Nephrology at the Institute of Nephro Urology, Bengaluru, evaluated the histopathological spectrum of DN and correlated clinical parameters with histological classes.
Therefore, the retrospective observational study evaluated 115 histologically diagnosed diabetic nephropathy (DN) cases out of 598 native kidney biopsies performed in 2023 at a tertiary center in Bengaluru, excluding samples with fewer than 10 glomeruli or missing immunofluorescence cores. Utilizing light microscopy and direct immunofluorescence evaluated per 2010 Renal Pathology Society (RPS) criteria, researchers assessed class distribution and correlated key clinical markers—including serum creatinine, proteinuria, and Interstitial Fibrosis and Tubular Atrophy (IFTA) scores—using IBM SPSS software.
Key Clinical Findings of the Study Includes:
- Predominance of Advanced Class IV Disease: The investigation revealed that Class IV advanced diabetic glomerulosclerosis predominated at 50.4% (58 cases), followed by Class III at 26.1% (30 cases), Class IIb at 9.9% (10 cases), and Class IIa at 2.97% (3 cases). • Significant Creatinine Elevation with Progression: The study demonstrated a significant increase in mean serum creatinine from 3.03 ± 2.57 mg/dL in Class IIa to 7.13 ± 3.48 mg/dL in Class IV (P < 0.001).
- Heavy Proteinuria Across Advanced Classes: The analysis identified that 24-hour urinary protein peaked in Class III at 7.81 ± 5.06 g/day compared to 1.46 ± 0.85 g/day in Class IIa (P = 0.001), with 95.6% showing severely increased albuminuria (>300 mg/g).
- Coexistence of Superimposed Non-Diabetic Lesions: The research detected superimposed NDRD in 12.2% of biopsies (14 cases), with IgA nephropathy being the most common co-existing pathology at 28.57% (4 cases).
- Divergence Between Clinical Duration and Structural Damage: The evaluation found no significant correlation between histological DN class and diabetes mellitus duration (mean 9.6 ± 5.4 years, P = 0.199), proving clinical duration does not predict structural severity.
The results suggest that advanced renal damage, dominated by Class IV lesions in 50.4% of patients, markedly impacts key clinical parameters like serum creatinine (5.53 ± 3.77 mg/dL) and daily proteinuria (5.69 ± 4.9 g/day). Because clinical disease duration fails to reflect underlying structural injury, renal biopsy remains essential for precise staging.
Thus, the study concludes clinicians should consider renal biopsy in diabetic patients presenting with atypical features or rapid renal decline, as histopathological evaluation helps identify coexisting non-diabetic lesions and guides management to delay End-Stage Kidney Disease (ESKD).
Although single-center selection bias, lack of electron microscopy for Class I detection, and incomplete retinopathy records introduce potential limitations, these insights highlight the need for prospective longitudinal studies to validate temporal disease progression.
Reference
Vinay KS, Somanath N, Mythri S, Shreedhar CG. Histopathological landscape of diabetic nephropathy: Insights from native kidney biopsies at a tertiary care centre in South India. Indian J Pathol Oncol. 2026;13(3):219-224.
