Abstract

Relevance. Diabetic nephropathy significantly impairs patients’ quality of life, leads to loss of working capacity, and is associated with high mortality. Current scientific trends demonstrate a transition from a conventional approach focused solely on normalising blood glucose levels towards developing comprehensive preventive strategies that block pathogenetic mechanisms directly at the molecular level.

Aim. To investigate the impact of the protein kinase inhibitor sorafenib on the histological structure of the kidney in a model of type 2 diabetes mellitus and during treatment.

Materials and methods. An experimental study was conducted on laboratory rats to model diabetes using a hypercaloric, high-fat diet for 150 days, followed by the induction of diabetes mellitus with streptozotocin. The animals were divided into the following experimental groups and subgroups: Group I: normal-calorie diet. Group II: diabetes modelling comprising subgroups IIa (placebo treatment), IIb (sorafenib treatment), IIc (insulin treatment) and IId (combined insulin and sorafenib treatment). Treatment following the induction of diabetes lasted for 30 days. The animals’ kidneys were then examined using general histological and morphometric methods. Paraffin sections were stained with haematoxylin and eosin. The areas of the renal corpuscles and glomeruli, as well as the cell density within the glomeruli, were measured.

Results. Animals in the experimental subgroups IIa, IIb and IIc exhibited moderate changes that predominantly affected the glomeruli. This was manifested by an increase in the glomerular area compared to that of intact animals. Animals in subgroup IIa were more frequently characterised by the presence of both obliterated and dilated capillaries. These capillaries were found within the glomerular loops. In animals in subgroups IIb and IIc, enlargement of the glomeruli was accompanied by dilatation of the capillary loops. The histological structure and morphometric parameters of the renal glomeruli in animals in subgroup IId were similar to those observed in group I. The morphological changes identified in subgroups IIa, IIb and IIc are characteristic of the early stages of diabetic nephropathy, indicating compression of the capillaries due to mesangial expansion and excessive dilatation of other capillaries as a result of hyperfiltration.

Conclusions. Using the protein kinase inhibitor sorafenib alongside the standard insulin therapy regimen prevented the development of the renal glomerular lesions characteristic of diabetic nephropathy.