Idiopathic nodular glomerulosclerosis and diabetic nephropathy: a histological and prognostic comparison highlighting the impact of smoking

Abstract Introduction Idiopathic nodular glomerulosclerosis (ING) and diabetic nephropathy (DN) display (almost) identical kidney biopsy findings. Our aim was to investigate potential disparities in histology and clinical outcomes, stratified by smoking status, in a Belgian cohort. Methods This retrospective case-control study included 64 patients with DN and 11 with ING. Eleven DN patients were matched with 11 ING patients for histological analysis based on sex, age, and histological lesions. Clinical and histological characteristics were compared using parametric and nonparametric methods. Estimated glomerular filtration rate (eGFR) decline and overall survival were assessed using linear mixed modelling with random intercepts and Kaplan-Meier survival analysis, respectively, stratified by smoking. Results Light microscopy revealed a trend toward more ischemic collapse in ING versus DN (36.4% vs. 0%, p = 0.090). Aberrant vessels were distributed differently between groups, being present in all ING cases but absent in 27.3% of DN cases (p = 0.045). Overall survival of smoking ING patients was lower compared with smoking DN patients (p = 0.010). The rate of eGFR decline was comparable between DN and ING (-5.41 versus − 6.27 ml/min/1.73 m² per year, p = 0.322). However, active smokers overall had a significantly faster decline in eGFR (p < 0.001). Conclusions Histology analysis confirmed that ING and DN share similar features, however subtle differences exist, with distribution of aberrant vessels being different in ING. Clinically, active smokers had worse outcomes in ING, despite no difference in GFR decline between DN and ING groups.