Molecular features of nephropathy associated with disorder of urate metabolism

Introduction: Urate nephrolithiasis is a common form of urolithiasis. The development of new methods for pharmacological correction of this disorder requires their practical laboratory assessment. So far, it is necessary to determine the most typical biochemical and histological signs of pathology. Aim: to study the biochemical and morphological features of experimental urate nephropathy. Methods: the experiment was carried out on 25 male Wistar rats weighing 200-330 grams, randomized into a group of intact rats (10 animals) and a control group (15 animals), in which a mixture of oxonic and uric acids was administered daily for 21 days to simulate urate nephrolithiasis. The excretion of uric acid and creatinine, the activity of lactate dehydrogenase and γ-glutamyl transferase were determined weekly in the urine of rats. At the end of the three weeks of the experiment, the indices of free radical oxidation (concentration of thiobarbiturate-reactive products, total prooxidant and total antioxidant activity, catalase, superoxide dismutase, glutathione peroxidase activity) were determined in the kidneys of rats and a morphological study was performed. Results: In intact rats, the activity of lactate dehydrogenase and γ-glutamyl transferase was stable, and in the control group, by day 21, the activity of lactate dehydrogenase increased by 6.3 times relative to the initial level and 3.8 times compared with the group of intact rats. The activity of γ-glutamyl transferase decreased by 2.6 and 3.4 times, respectively. In the control group, the concentration of thiobarbiturate- reactive products and the total antioxidant activity increased relatively in intact rats (by 3.3 times and 1.8 times, respectively), while the catalase activity was reduced by 5.1 times. Urate deposits were absent in intact rats’ kidneys. In the control group, urate deposits were detected in 76.9% of cases, their average amount was 4.2±0.8 in the field of view, and their average size was 1340.5±211.1 μm2. Conclusion: the histopathological picture of experimental urate nephropathy is characterized by increase in lactate dehydrogenase activity and decrease in γ-glutamyl transferase activity in urine, the oxidative stress and urate deposits in the kidneys

urate nephrolithiasis, biochemical picture, histological picture