Ruolo del tubulo renale nella patogenesi della nefropatia diabetica: analisi morfometrica mediante microscopia ottica ed elettronica in pazienti di tipo 2

In type 1 diabetes (D1) nephropathy is characterized by glomerular and tubulo-interstitial structural abnormalities. In type 2 diabetes (D2) histological picture is more heterogeneous and in a large proportion of patients tubulo-interstitial structural changes are present in absence of glomerular damage, suggesting an important role of tubular lesions in the pathogenesis of diabetic nephropathy. Aims: to measure in D2 patients with different albumin excretion rate (AER) levels proximal tubular basement membrane width (TBM width), interstitial expansion [Vv(Int/cortex)], the proportion of atrophic tubules [Vv(Ta/Tt)], the proportion of cytoplasmic empty spaces in tubular cells [Vv(ES/cit)], and the relationships with GBM width, Vv(mes/glom) and renal functional parameters. Matherals and methods: In 42 D2 (16 normoalbuminuric-NA, 16 microalbuminuric-MA and 10 proteinuric-P) HbA1c, albumin excretion rate (AER), glomerular filtration rate (GFR) (plasma clearance of 51Cr-EDTA) and blood pressure were evaluated. Kidney biopsy was performed and by electron and light microscopy TBM and GBM width, Vv(ES/cit), Vv(mes/glom), Vv(Int/cortex) and Vv(Ta/Tt) were evaluated. Results: diabetes duration, BMI, HbA1c, blood pressure and GFR did not differed between groups. TBM width increased in the 3 groups (707±177 nm in NA, 875±225 in MA, 1055±169 in P, Anova < 0.001); GBM width, Vv(mes/glom) and Vv(Ta/Tt) were increased in P than in NA and MA (p<0.005 NA vs P e p<0.05 MA vs P). In P Vv(int/cortex) values were increased when compared with MA (p < 0.05 MA vs P). Vv(ES/cit) values were similar in the 3 groups. Regression analysis showed a direct correlation between TBM width, GBM width (r=0.53, p<0.001) and Vv(mes/glom) (r=0.475, p<0.01). Also Vv(Ta/Tt) was related to GBM width (r=0.48, p<0.01) and Vv(mes/glom) (r=0.64, p<0.0001). Vv(int/cortex) was correlated only to Vv (mes/glom) (r=0.43, p<0.05). Multiple regression analysis between AER and all structural parameters showed a significant correlation only between AER and TBM width (Beta = 0.40, p<0.05). TBM width and HbA1c were also related (r=0.41, p<0.01). Conclusions: TBM thickening is present in D2 patients and plays an important role in the pathogenesis of abnormal AER in these patients. The correlation between TBM width and HbA1c suggests a direct role of hyperglycemia in the pathogenesis of tubular damage.