PATHOPHYSIOLOGY OF PROTEINURIA IN THE DYNAMICS OF ALLOXAN-INDUCED EXPERIMENTAL DIABETES

Abstract

Summary. Diabetic kidney disease (DKD) is a clinical diagnosis that has historically been based on the detection of proteinuria in a patient with diabetes mellitus, and until recently, proteinuria was thought to reflect the extent of glomerular disease in the diabetic kidney. Micro- and macroalbuminuria are associated with a progressive decrease in glomerular filtration rate, increased systemic blood pressure, and a high risk of developing renal failure.

The aim of the study – to explore the pathophysiology of proteinuria in the dynamics of alloxan-induced experimental diabetes mellitus.

Materials and Methods. The experiments were carried out on 63 white non-linear mature male rats, 53 with experimental diabetes mellitus (EDМ) of varying duration induced by intraperitoneal administration of alloxan at a dose of 160 mg/kg of body weight, 10 intact rats served as the control group. 10, 20, 25, 30, 40 and 45 days after administration of the diabetogenic substance, the animals were withdrawn from the experiment.

Results. The study of excretory function of the kidneys was provided by the clearance method under the condition of water induced 2-hour diuresis to determine the clearance of endogenous creatinine, glomerular filtration rate, protein content in urine, its excretion, including standardized by glomerular filtrate volume. The protein content in the urine of experimental animals, as well as parameters of protein excretion with the urine, significantly exceeded control values at all stages of alloxan-induced diabetes, developing against the background of hyperfiltration. Protein excretion, standardized by the glomerular filtrate volume, increased significantly only in 11-day alloxan diabetes, decreasing from the 21st to the 31st day of the experiment. The tendency to raise the standardized urine excretion of protein from the 41st day of the experiment maximally developed in 46-day long EDМ.

Conclusions. The results of the study allow concluding that the initial stages of alloxan-induced experimental diabetes are accompanied by hemodynamic-hyperperfusion type of renal function, and intensification of protein excretion is a consequence of hyperfiltration against the background of structural and functional preservation of the glomerular-tubular apparatus of the kidney. Mentioned compensatory-functional renal disorders in 26-day long experimental diabetes are complicated by depletion of the functional renal reserve and the development of tubulopathies. Further exposure to hyperfiltration in 46-day long experimental diabetes leads to changes in the architectonics and increased permeability of the glomerular basement membrane for protein and the development of glomerular albuminuria.