Pathophysiology of diabetic nephropathy: Pathophysiology of diabetic nephropathy

Gulden Yildiz; Kubra Kaya

doi:10.5281/zenodo.10444772

Authors

Gulden Yildiz Kafkas University, Faculty of Medicine, Department of Pathology, Kars Türkiye https://orcid.org/0000-0003-1530-8529
Kubra Kaya Kafkas University, Faculty of Veterinary Medicine, Department of Physiology, Kars Türkiye https://orcid.org/0009-0004-8702-0772

DOI:

https://doi.org/10.5281/zenodo.10444772

Keywords:

Diabetic nephropathy, hyperglycemia, pathophysiology

Abstract

Glomerular basement membrane thickening is common in patients with long-standing diabetes, with or without nephropathy. In the following period, there is a correlation between glomerular basement membrane thickness and fractional mesangial volumes and albuminuria. The mechanisms underlying the formation of albuminuria begin with expansion of the glomerular basement membrane (GBM) with deposition of type IV collagen and reduction of negatively charged heparin sulfate proteoglycan. One of the earliest cellular changes in diabetes is mesangial and tubular cell hypertrophy. Hyperglycemia causes hypertrophy in the kidney by stimulating growth factors such as insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), VEGF, TGF-β and Ang II. However, antagonizing TGF-β in diabetic patients did not provide beneficial effects on renal function or proteinuria. Pathological features of diabetic nephropathy (DN) are mesangial expansion, nodular diabetic glomerulosclerosis (acellular Kimmelstiel-Wilson lesion), and diffuse glomerulosclerosis. Kidney structure is heterogeneous in diabetic patients; Only a subset of patients have typical diabetic glomerulopathy, whereas others have tubulointerstitial and vascular lesions that are much more advanced than glomerular lesions. There are features suggestive of normal or near-normal kidney structure and even glomerular ischemia. Treatment of diabetic animals with an ACE inhibitor attenuates p27 Kip1 and reduces renal hypertrophy.

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Pathophysiology of diabetic nephropathy