Abstract:

Histological alterations observed in diabetic kidney disease (DKD) comprise a wide range of structural changes, including mesangiolysis, expansion of the mesangial matrix, proliferation of mesangial cells, thickening of the glomerular basement membrane, podocyte depletion, effacement of foot processes, and hyalinosis of glomerular arterioles. In addition, interstitial fibrosis, tubular atrophy, and glomerulomegaly are common findings. Importantly, histopathological evidence of DKD may appear even when clinical indicators are still within normal limits — for example, in individuals with normal urinary albumin levels and preserved glomerular filtration rate. Over time, histological damage tends to progress, while clinical parameters may remain unchanged.

Interestingly, structural abnormalities in DKD can improve after successful pancreas transplantation, which restores metabolic control. Insulin resistance plays a significant role in the pathogenesis of DKD and is linked with its clinical expressions such as kidney enlargement, glomerular hyperfiltration, albuminuria, and progressive renal failure. This resistance is also believed to contribute to the underlying histological damage. In patients newly diagnosed with type 1 diabetes — who initially lack insulin resistance — morphological changes are typically absent but tend to emerge as insulin resistance develops later. Conversely, in type 2 diabetes, structural lesions of DKD often precede the clinical onset of the disease.

A number of other insulin-resistant conditions — including aging, obesity, acromegaly, lipodystrophy, cystic fibrosis, insulin receptor abnormalities, and Alström syndrome — also display similar renal clinical and structural abnormalities, such as glomerulomegaly, focal segmental glomerulosclerosis, and C3 glomerulopathy. These conditions may share a common mechanism involving decreased synthesis of factor H binding sites (e.g., heparan sulfate), resulting in unregulated complement activation. Notably, Alström syndrome is characterized by systemic interstitial fibrosis that closely resembles that seen in diabetic patients.