INFLUENCE OF CHRONIC HYPERGLYCEMIA ON THE DEVELOPMENT OF TUBULOINTERSTITIAL SYNDROME IN EXPERIMENTAL DIABETES MELLITUS

Abstract

Summary. Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus, the main role in the development and progression of which is played by untreated or insufficiently corrected hyperglycemia, the duration and magnitude of which correlate well with the degree and rate of diabetic kidney disease. Prolonged hyperglycemia triggers a number of metabolic disorders and, ultimately, leads to a progressive decrease in the mass of active nephrons.

The aim of the study – to explore the mechanisms of tubulointerstitial syndrome formation with underlying chronic  alloxan-induced hyperglycemia.

Materials and Methods. The experiments were carried out on 20 white non-linear mature male rats, 10 with experimental diabetes mellitus (EDМ) induced by intraperitoneal administration of alloxan at a dose of 160 mg/kg of body weight, 10 intact rats served as the control group. 45 days after administration of the diabetogenic substance, the animals were withdrawn from the experiment. Statistical processing of the obtained data was carried out with the determination of the mean value, standard deviations. To assess the probability of the difference between the experimental groups used non-parametric ranking criterion Mann–Whitney according to the algorithms implemented in the computer program "Statistica for Windows", "Version 8.0". The research was conducted in compliance with the provisions of the Council of the European Communities Directive  No. 609 (1986) and the order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 "On measures to further  improve the organizational standards of work with the use of experimental animals".

Results. The papillary-cortical and medullary-cortical concentration sodium gradients were found to be significantly increased, while the papillary-medullar sodium gradient was reliably decreased. Similar changes concerned the concentration potassium renal gradients. Meanwhile, the concentration of sodium and potassium ions in the urine of alloxandiabetic animals and the intensity of their excretion rose. Enhanced renal filtration sodium load was accompanied by an increase in proximal sodium reabsorption, but standardized in volume of glomerular filtrate, its level as well as distal cation transport level, were found to be lower as compared to the control indices. Though the relative reabsorption of sodium ions remained practically unchanged, it was accompanied by a significant elevation of cation clearance. In urine and blood plasma samples, glucose levels were determined, as well as the concentration of sodium and potassium ions, followed by calculation (taking into account water-induced 2-hour diuresis and endogenous creatinine clearance) of electrolyte excretion, filtration intensity, absolute and relative reabsorption. index, their proximal and distal renal flow. The kidneys removed after decapitation of rats were stratified into 3 parts – cortical and cerebral substance, renal papillae, in the aqueous extract of the corresponding part of the renal parenchyma determined the concentration of sodium and potassium ions, calculated papillary-cortical, papillary-cerebral and cerebral-cortical.

Conclusions. Chronic alloxan-induced hyperglycemia causes the development of tubulointensive disorders, the manifestations of which are observed long before the manifestation of glomerulopathy. Caused by hyperperfusion-hyperfiltration overload of the kidneys, the depletion of the reabsorption capacity of the tubular apparatus of the kidneys is reflected on both the proximal and distal tubules, and initiates a violation of the reabsorption processes and ionouresis. It is disorders of the tubular supply of sodium and potassium ions, redistribution of their content between the vascular, tubular and interstitial compartments of the kidneys, lead to local hemodynamics in the kidneys, changes in hydrophilicity and osmolarity of the interstitium, limiting regulatory effects of reversible multiplication system regulation of water-osmotic balance.