Molecular features of nephropathy associated with disorder of urate metabolism


A.S. Kalnitsky, A.Yu. Zharikov, O.N. Mazko, O.G. Makarova, I.P. Bobrov Altay State Medical University, Lenina Street, 40, Barnaul, Russian Federation, 656038 E-mail: [email protected]

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

Список литературы: 
  1. Sakhaee K. Epidemiology and clinical pathophysiology of uric acid kidney stones. J. Nephrol. 2014; 27: 241–5.
  2. Ferraro P.M., Gambaro G. Calcolosi uratica. Giornale Italiano Di Nefrologia. 2015; 32: 62 (In Italian). PMID: 26005875
  3. Spatola L., Ferraro P.M., Gambaro G., Badalamenti S., Dauriz M. Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus. Metabolism. 2018; 83: 225–33.
  4. Kaprin A.D., Kostin A.A., Ivanenko K.V., Popov S.V. Sovremennye issledovanija effektivnosti tsitratnoj terapii uratnogo nefrolitiaza v Rossii. Meditsinskij sovet. 2017; 11: 176–80. [Kaprin A.D., Kostin A.A., Ivanenko K.V., Popov S.V. Surrent studies of the efficacy of citrate therapy for uric acid nephrolithiasis in Russia. Meditsinskiy sovet. 2017; 11: 176–80 (In Russian).]
  5. Perfil'ev V.Ju., Zverev Ja.F., Zharikov A.Ju., Uslovija razvitija uratnogo nefrolitiaza i podhody k ego modelirovaniju. Nefrologija. 2017; 21 (4): 48–54. [Perfilev V.Yu., Zverev Y.F., Zharikov A.Yu. Sonditions of urate nephrolithiasis and approaches to its modeling. Nefrologiya. 2017; 21 (4): 48–54 (In Russian)]
  6. Brjuhanov V.M., Zverev Ja.F., Lampatov V.V., Zharikov A.Ju., Talalaeva O.S. Metody doklinicheskogo (eksperimental'nogo) issledovanija vlijanija lekarstvennyh sredstv na funktsiju pochek. Novosibirsk. Geo. 2013; 84. [Bryukhanov V.M., Zverev Ya.F., Lampatov V.V., Zharikov A.Yu., Talalaeva O.S. Metody doklinicheskogo (ehksperimental’nogo) issledovaniya vliyaniya lekarstvennykh sredstv na funktsiyu pochek (Methods of preclinical (experimental) study of the effect of drugs on renal function). Novosibirsk. Geo. 2013; 84 (In Russian)]
  7. Hafiz'janova R.H., Burykin I.M., Aleeva G.N. Matematicheskaja statistika v eksperimental'noj i klinicheskoj farmakologii. Kazan': Meditsina, 2006; 374. [Khafizyanova R.Kh., Burikin I.M., Aleeva G.N. Matematicheskaya statistika v eksperimental’noy i klinicheskoy farmakologii. (Mathematical statistics in experimental and clinical pharmacology.) Kazan: Meditsina, 2006; 374 (In Russian)]
  8. Kabakov A.E., Gabai V.L. Cell Death and Survival Assays. Methods Mol. Biol. 2018; 1709: 107–27.
  9. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem. 2017; 524: 13–30.
  10. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free. Radic. Biol. Med. 2000; 29 (11): 1106–14.
  11. Sepasi Tehrani H, Moosavi-Movahedi A.A. Catalase and its mysteries. Prog Biophys Mol Biol. 2018; 140: 5–12.