Disorder of purine metabolism in the etiopathogenesis of urate nephrolithiasis

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.1.273835

Keywords:

urolithiasis, urate nephrolithiasis, hyperuricemia, uric acid, kidney damage, purine metabolism

Abstract

Urinary stone disease (USD) is a polyetiological urological disease caused by both exogenous and endogenous factors, including hereditary ones. It is characterized by the appearance of stones in the kidneys and urinary tract, and a tendency to relapse, often with a severe course. Almost 25 % of stones consist of uric acid (UA). The leading role in the pathogenesis of urate nephrolithiasis (UN) is played by disorders of purine metabolism, which are characterized by the development of hyperuricemia (HU) and hyperuricuria.

The aim of the work is to review modern literary sources on the role of purine metabolism disorders in the etiopathogenesis of UN.

Results. The development of UN depends on the constancy of the acidic urine pH, as well as on a decrease in diuresis, HU and hyperuricuria. UA is the final metabolite of purine metabolism and the main stone-forming substance in patients with UN. HU develops both due to uncompensated disorders of purine metabolism with a decrease in renal secretion and intestinal uricolysis (excretion pathway) and excessive intake of purine bases in the body and their increased synthesis in vivo (metabolic pathway).

Citric acid, as one of the main metabolites of the tricarboxylic acid (TCA) cycle, is connected through the corresponding substrates to the formation of purines and the metabolite of amino acid metabolism, glutamine. TCA is connected to the cycles of urea, glyoxylate and purine bases through α-ketaglutaric acid. It is a substrate of citric acid, and it affects the synthesis of glutamate, which combines with ammonia to form glutamine, used in the cycle of purine synthesis.

Conclusions. The role and diagnostic value of purine metabolism upsets, disorders of the TCA (citric acid), amino acid metabolism (glutamine), the activity of xanthine oxidase is a key enzyme in purine synthesis which passes through TCA with the participation of its metabolite α-ketaglutarate, have been established. TCA is bound to glutamine, rich in nitrogen, which is necessary for the synthesis of purine bases.

Author Biographies

S. I. Vorotyntsev, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Anesthesiology and Intensive Care

A. I. Bilai, Zaporizhzhia State Medical University, Ukraine

MD, PhD, Assistant of the Department of Faculty Surgery

I. M. Bilai, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy, and Pharmaceutical Chemistry

References

Sergeeva, L., Bachurin, G. Strogonova, T., & Kolomoets, Yu. (2021). Diskriminantnyi analiz kak metod podderzhki prinyatiya resheniya v meditsinskikh issledovaniyakh na primere immunofermentnogo analiza u bolnykh mochekamennoi boleznyu [Discriminant analysis as a supporting method of decision-making in medical investigations on the example of the enzyme immunoassay in patients with urolithiasis]. Georgian Medical News, (7-8), 147-153. [in Russian].

Heers, H., & Turney, B. W. (2016). Trends in urological stone disease: a 5-year update of hospital episode statistics. BJU international, 118(5), 785-789. https://doi.org/10.1111/bju.13520

Vozianov, O. S. (2021). Rezultaty likuvannia khvorykh na ureterolitiaz metodom ekstrakorporalnoi udarno-khvylovoi litotrypsii na aparati Siemens Modularis Uro [Results of treatment of patients with ureterolithiasis by extracorporal shock wave lithotripsy on Siemens Modularis Uro]. Zdorovia cholovika, (1), 24-26. [in Ukrainian].

Chernenko V. V., Chernenko D. V., Zheltovska N. I., & Savchuk V. I. (2017). Mochekislaya giperkristalluriya i ee rol v formirovanii pochechnykh konkrementov [Urate hypercrystalluria and its role in formation of renal concrements]. Urolohiia, 21(1), 6-9. [in Russian].

Vozianov, S. O., Sahalevych, A. I., Boiko, A. I., Haiseniuk, F. Z., Kohut, V. V., Dzhuran, B. V., & Sosnin, M. D. (2021). Suchasnyi pohliad na bezdrenazhnu perkutannu nefrolitotrypsiiu [A modern view on tubeless percutaneous nephrolithotomy]. Zaporozhye medical journal, 23(4), 575-582. [in Ukrainian]. https://doi.org/10.14739/2310-1210.2021.4.226895

Vozianov, S. O., Saidakova, N. O., & Startseva, L. N. (2013). Stan ta perspektyvy rozvytku urolohichnoi sluzhby v Ukraini [The state and perspectives for the development of the urologic service in Ukraine]. Urolohiia, 17(3), 89-95. [in Ukrainian].

Chernenko, V. V., & Chernenko, D. V. (2015). Pidvyshchennia efektyvnosti reabilitatsii u khvorykh na sechokamianu khvorobu pislia provedennia litotrypsii [Improving the efficiency of the rehabilitation of patients with urolithiasis after lithotripsy]. Urolohiia, 19(4), 14-20. [in Ukrainian].

Stus, V. P., Moiseenko, N. N., Zhbakov, M. V., &Ehalov, V. V. (2020). Vliyanie alimentarnykh faktorov na rN mochi [Effect of alimentral factors on urine pH]. Urologiya, 24(4), 335-343. [in Ukrainian].

Bachurin, H., & Kolomoiets, Yu. (2020). Rezultaty vykorystannia predyktoriv zapalennia u khvorykh na sechokamianu khvorobu [Results of application of predictors of inflammation in patients with urolithiasis]. Zdorovia cholovika, (1), 71-74. [in Ukrainian].

Chernenko, V. V., Savchuk, V. Y., Zheltovska, N. I., Chernenko, D. V., & Bondarenko, Yu. M. (2019). Novi mozhlyvosti v korektsii hiperurykemii u khvorykh na sechokamianu khvorobu ta sechokyslu hiperkrystaluriiu [Current possibilities in the correction of hyperuricemia in patients with urolithiasis and uric acid hypercrystallization]. Zdorovia cholovika, (3), 70-74. [in Ukrainian].

Pearle, M. S., Goldfarb, D. S., Assimos, D. G., Curhan, G., Denu-Ciocca, C. J., Matlaga, B. R., Monga, M., Penniston, K. L., Preminger, G. M., Turk, T. M., White, J. R., & American Urological Assocation (2014). Medical management of kidney stones: AUA guideline. The Journal of urology, 192(2), 316-324. https://doi.org/10.1016/j.juro.2014.05.006

Leanez Jiménez, M., Candau Vargas-Zúñiga, F., & Reina Ruiz, C. (2017). La litiasis urinaria como enfermedad sistémica [Urinary lithiasis as a systemic disease.]. Archivos espanoles de urologia, 70(1), 28-39.

Romero, V., Akpinar, H., & Assimos, D. G. (2010). Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Reviews in urology, 12(2-3), e86-e96.

Oh, C., Kim, H. S., & No, J. K. (2015). Impact of dining out on nutritional intake and metabolic syndrome risk factors: data from the 2011 Korean National Health and Nutrition Examination Survey. The British journal of nutrition, 113(3), 473-478. https://doi.org/10.1017/S0007114514003870

Fink, H. A., Wilt, T. J., Eidman, K. E., Garimella, P. S., MacDonald, R., Rutks, I. R., Brasure, M., Kane, R. L., Ouellette, J., & Monga, M. (2013). Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Annals of internal medicine, 158(7), 535-543. https://doi.org/10.7326/0003-4819-158-7-201304020-00005

Ernandez, T., Stoermann Chopard, C., Bonny, O., Iselin, C., Martin, P. Y., & Jaeger, P. (2013). Approche pratique de la lithiase rénale: duo entre généralistes et spécialistes [Renal stone disease: collaborative management between primary care and specialized physicians]. Revue medicale suisse, 9(375), 456-461.

Moses, R., Pais, V. M., Jr, Ursiny, M., Prien, E. L., Jr, Miller, N., & Eisner, B. H. (2015). Changes in stone composition over two decades: evaluation of over 10,000 stone analyses. Urolithiasis, 43(2), 135-139. https://doi.org/10.1007/s00240-015-0756-6

Türk, C., Petřík, A., Sarica, K., Seitz, C., Skolarikos, A., Straub, M., & Knoll, T. (2016). EAU Guidelines on Interventional Treatment for Urolithiasis. European urology, 69(3), 475-482. https://doi.org/10.1016/j.eururo.2015.07.041

El-Gamal, O., El-Bendary, M., Ragab, M., & Rasheed, M. (2012). Role of combined use of potassium citrate and tamsulosin in the management of uric acid distal ureteral calculi. Urological research, 40(3), 219-224. https://doi.org/10.1007/s00240-011-0406-6

European Association of Urology. (2022). EAU Guidelines on Urolithiasis. https://uroweb.org/guidelines/urolithiasis

Bhadoria, A. (2015). Metabolic syndrome and associated risk factors. Journal of Family and Community Medicine, 22(1), 57. https://doi.org/10.4103/2230-8229.149593

Syniachenko, O. V. Ihnatenko, T. A., & Mukhin, I. V. (2004). Kliniko-laboratorni aspekty purynovoho obminu: norma i patolohiia [Clinic-laboratory aspects of the purine exchange: the norm and pathology]. Medytsyna zaliznychnoho transportu Ukrainy, (1), 96-100. [in Ukrainian].

Ng, H. Y., Leung, F. F., Kuo, W. H., Lee, W. C., & Lee, C. T. (2021). Dapagliflozin and xanthine oxidase inhibitors improve insulin resistance and modulate renal glucose and urate transport in metabolic syndrome. Clinical and experimental pharmacology & physiology, 48(12), 1603-1612. https://doi.org/10.1111/1440-1681.13574

Li, L., Zhang, Y., & Zeng, C. (2020). Update on the epidemiology, genetics, and therapeutic options of hyperuricemia. American journal of translational research, 12(7), 3167-3181.

Bonino, B., Leoncini, G., Russo, E., Pontremoli, R., & Viazzi, F. (2020). Uric acid in CKD: has the jury come to the verdict?. Journal of nephrology, 33(4), 715-724. https://doi.org/10.1007/s40620-020-00702-7

Sanchez-Lozada, L. G., Rodriguez-Iturbe, B., Kelley, E. E., Nakagawa, T., Madero, M., Feig, D. I., Borghi, C., Piani, F., Cara-Fuentes, G., Bjornstad, P., Lanaspa, M. A., & Johnson, R. J. (2020). Uric Acid and Hypertension: An Update With Recommendations. American journal of hypertension, 33(7), 583-594. https://doi.org/10.1093/ajh/hpaa044

Lee, S. J., Oh, B. K., & Sung, K. C. (2020). Uric acid and cardiometabolic diseases. Clinical hypertension, 26, 13. https://doi.org/10.1186/s40885-020-00146-y

Skolarikos, A., Straub, M., Knoll, T., Sarica, K., Seitz, C., Petřík, A., & Türk, C. (2015). Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. European urology, 67(4), 750-763. https://doi.org/10.1016/j.eururo.2014.10.029

Letendre, J., Cloutier, J., Villa, L., & Valiquette, L. (2015). Metabolic evaluation of urinary lithiasis: what urologists should know and do. World journal of urology, 33(2), 171-178. https://doi.org/10.1007/s00345-014-1442-y

Copur, S., Demiray, A., & Kanbay, M. (2022). Uric acid in metabolic syndrome: Does uric acid have a definitive role?. European journal of internal medicine, 103, 4-12. https://doi.org/10.1016/j.ejim.2022.04.022

Marchini, G. S., Sarkissian, C., Tian, D., Gebreselassie, S., & Monga, M. (2013). Gout, stone composition and urinary stone risk: a matched case comparative study. The Journal of urology, 189(4), 1334-1339. https://doi.org/10.1016/j.juro.2012.09.102

Published

2023-03-10

How to Cite

1.
Vorotyntsev SI, Bilai AI, Bilai IM. Disorder of purine metabolism in the etiopathogenesis of urate nephrolithiasis. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Mar.10 [cited 2024Oct.6];16(1):90-7. Available from: http://pharmed.zsmu.edu.ua/article/view/273835

Issue

Section

Review