The Role of Hyperuricemia in the Pathogenesis and Progressivity of Chronic Kidney Disease

Gede Wira Mahadita; Ketut Suwitra

doi:10.3889/oamjms.2021.7100

Authors

Gede Wira Mahadita Department of Internal Medicine, Nephrology and Hypertension Division, Faculty of Medicine, Udayana University, Sanglah General Hospital, Denpasar, Bali, Indonesia https://orcid.org/0000-0002-8165-5046
Ketut Suwitra Department of Internal Medicine, Nephrology and Hypertension Division, Faculty of Medicine, Udayana University, Sanglah General Hospital, Denpasar, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7100

Keywords:

Hyperuricemia, Chronic kidney disease, Pathogenesis, Progressivity

Abstract

In humans, the end product of purine metabolism is uric acid. Over 70% of uric acid is excreted through the kidneys. When renal function is impaired, uric acid secretion is also impaired. This directly correlates the prevalence of hyperuricemia with the severity of chronic kidney disease (CKD). It has been reported that the prevalence of hyperuricemia in patients with Stage I-III CKD is 40–60% and up to 70% in patients with Stage IV-V CKD. Some studies found a link between serum uric acid levels and decreased glomerular filtration rate (GFR), an independent risk factor for CKD development. Because CKD and serum uric acid levels are related, the relationship between the two frequently generates controversy. As such, this review of the literature discusses the role of uric acid in the pathogenesis and progression of CKD.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Peronato G. Purine metabolism and hyperuricemic states. In: Ronco C, Rodeghiero F, editors. Hyperuricemic Syndromes: Pathophysiology and Therapy. Switzerland: Karger; 2005. p. 1-21. DOI: https://doi.org/10.1159/000082538

Zhu Y, Pandya BJ, Choi HK. Prevalence of Gout and hyperuricemia in The US general population: The national health and nutrition examination survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-41. https://doi.org/10.1002/art.30520 PMid:21800283 DOI: https://doi.org/10.1002/art.30520

Dharmawan J, Valkenburg HA, Muirden KD, Wigley RD. The epidemiology of gout and hyperuricemia in rural population of java. J Rheumatol. 1992;19(10):1595-9. PMid:1464874

Indonesian Renal Registry. Report of Indonesian Renal Registry. 5th ed. Jakarta: Perhimpunan Nefrologi Indonesia; 2012. p. 1-40.

Nashar K and Fried LF. Hyperuricemia and the progression of chronic kidney disease: Is uric acid a marker or an independent risk factor? Adv Chronic Kidney Dis. 2012;19(6):386-91. https://doi.org/10.1053/j.ackd.2012.05.004 PMid:23089273 DOI: https://doi.org/10.1053/j.ackd.2012.05.004

Madero M, Sarnak MJ, Wang X, Greene T, Beck GJ, Kusek JW. Uric acid and long-term outcome in CKD. Am J Kidney Dis. 2009;53(5):796-803. https://doi.org/10.1053/j.ajkd.2008.12.021 PMid:19303683 DOI: https://doi.org/10.1053/j.ajkd.2008.12.021

Khanna D, Fitzgerald JD, Khanna PP. 2012 American college of rheumatology guideline for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64(10):1431-46. https://doi.org/10.1002/acr.21772 PMid:23024028 DOI: https://doi.org/10.1002/acr.21772

Hsu CY, Iribarren C, McCulloch CE. Risk factors for end-stage renal disease: 25 years follow-up. Arch Intern Med. 2009;169(4):342-50. https://doi.org/10.1001/archinternmed.2008.605 PMid:19237717 DOI: https://doi.org/10.1001/archinternmed.2008.605

Bellomo G, Venanzi S, Verdura C. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56(2):264-72. https://doi.org/10.1053/j.ajkd.2010.01.019 PMid:20385436 DOI: https://doi.org/10.1053/j.ajkd.2010.01.019

Obermayr RP, Temml C, Gutjahr G. Elevated uric acid increase the risk for kidney disease. J Am Soc Nephrol. 2008;19(12):2407-13. https://doi.org/10.1681/ASN.2008010080 PMid:18799720 DOI: https://doi.org/10.1681/ASN.2008010080

Weiner DE, Tighiouart H, Elsayed EF. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19(6):1204-11. https://doi.org/10.1681/ASN.2007101075 PMid:18337481 DOI: https://doi.org/10.1681/ASN.2007101075

Khang DH, Chen W. Uric acid and chronic kidney disease: New understanding of an old problem. Semin Nephrol. 2011;31(5):447-52. https://doi.org/10.1016/j.semnephrol.2011.08.009 PMid:22000652 DOI: https://doi.org/10.1016/j.semnephrol.2011.08.009

Feig DI, Kang DH, Johson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811-21. https://doi.org/10.1056/NEJMra0800885 PMid:18946066 DOI: https://doi.org/10.1056/NEJMra0800885

Hediger MA, Johnson RJ, Miyazaki H. Molecular physiology of urate transport. Physiology. 2005;20:125-33. https://doi.org/10.1152/physiol.00039.2004 PMid:15772301 DOI: https://doi.org/10.1152/physiol.00039.2004

Sah OM, Qing YK. Association between hyperuricemia and chronic kidney disease: A review. Nephrol Urol Mon. 2015;7(3):e27233. https://doi.org/10.5812/numonthly.7(3)2015.27233 PMid:26290849 DOI: https://doi.org/10.5812/numonthly.7(3)2015.27233

Choi HK, Mount DB, Reginato AM. Pathogenesis of Gout. Ann Intern Med. 2005;143(7):499-516. https://doi.org/10.3949/ccjm.75.suppl_5.s2 PMid:16204163 DOI: https://doi.org/10.7326/0003-4819-143-7-200510040-00009

Shirashi H, Une H. The effect of the interaction between obesity and drinking on hyperuricemia in Japanese male office workers. J Epidemiol. 2009;19(1):12-6. https://doi.org/10.2188/jea.je20080016 PMid:19164873 DOI: https://doi.org/10.2188/jea.JE20080016

Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adoloscent with newly diagnosed essential hypertension: A randomized trial. JAMA. 2008;300(8):924-32. https://doi.org/10.1001/jama.300.8.924 PMid:18728266 DOI: https://doi.org/10.1001/jama.300.8.924

Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M. A role for uric acid in the progression for renal disease. J Am Soc Nephrol. 2002;13(12):2888-97. https://doi.org/10.1097/01.asn.0000034910.58454.fd PMid:12444207 DOI: https://doi.org/10.1097/01.ASN.0000034910.58454.FD

Nakagawa T, Mazzali M, Kang DH. Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol. 2003;23:2-7. https://doi.org/10.1159/000066303 PMid:12373074 DOI: https://doi.org/10.1159/000066303

Han HJ, Lim MJ, Lee YJ, Lee JH, Yang IS, Taub M. Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathway involving PKC, MAPK, cPLA2 and NF-kappaB. Am J Physiol Renal Physiol. 2007;292(1):F373-81. https://doi.org/10.1152/ajprenal.00104.2006 PMid:16985215 DOI: https://doi.org/10.1152/ajprenal.00104.2006

Mazzali M, Kanellis J, Han L, Feng L, Xia YY, Chen Q. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002;282(6):F991-7. https://doi.org/10.1152/ajprenal.00283.2001 PMid:11997315 DOI: https://doi.org/10.1152/ajprenal.00283.2001

Kennelis J, Watanabe S, Li JH. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxigenase-2. Hypertension. 2003;41(6):1287-93. https://doi.org/10.1161/01.HYP.0000072820.07472.3B PMid:12743010 DOI: https://doi.org/10.1161/01.HYP.0000072820.07472.3B

Talaat KM, Sheikh AR. The effect of mild hyperuricemia on urinary transforming growth factor beta and the progression of chronic kidney disease. Am J Nephrol. 2007;27(5):435-40. https://doi.org/10.1159/000105142 PMid:17622758 DOI: https://doi.org/10.1159/000105142

Zeisberg M, Kalluri R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med. 2004;82(3):175-81. https://doi.org/10.1007/s00109-003-0517-9 PMid:14752606 DOI: https://doi.org/10.1007/s00109-003-0517-9

Lozada LG, Soto V, Tapia E, Casado C, Sautin YY, Nakagawa T. Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol. 2008;292(4):F1134-41. https://doi.org/10.1152/ajprenal.00104.2008 PMid:18701632 DOI: https://doi.org/10.1152/ajprenal.00104.2008

Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, et al. Is there a pathogenic role for uric acid in hypertension and cardiovascular disease? Hypertension. 2003;41(6):1183-90. https://doi.org/10.1161/01.HYP.0000069700.62727.C5 PMid:12707287 DOI: https://doi.org/10.1161/01.HYP.0000069700.62727.C5

Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101-6. https://doi.org/10.1161/hy1101.092839 PMid:11711505 DOI: https://doi.org/10.1161/hy1101.092839

Nangaku M. Chronic interstitial nephritis. In: Johnson RJ, Feehally J, Floege J, editors. Comprehensive Clinical Nephrology. 5th ed. Philadelphia, PA: Elsevier Saunders, 201. p. 746-58.

Goicoechea M, De Vinuesa SG, Vardalles U. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5(8):1388-93. https://doi.org/10.2215/CJN.01580210 PMid:20538833 DOI: https://doi.org/10.2215/CJN.01580210

Kanbay M, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I. A randomized study of allopurinol on endothelial function and estimated glomerular filtration rate in asymptomatic hyperuricemic subject with normal renal function. Clin J Am Soc Nephrol. 2011;6(8):1887-94. https://doi.org/10.2215/CJN.11451210 PMid:21784838 DOI: https://doi.org/10.2215/CJN.11451210

Terawaki H, Nakayama N, Miyazawa E. Effect of allopurinol on cardiovascular incidence among hypertensive nephropathy patients: The gonryo study. Clin Exp Nephrol. 2013;17(4):549-53. https://doi.org/10.1007/s10157-012-0742-z PMid:23192770 DOI: https://doi.org/10.1007/s10157-012-0742-z

Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47(1):51-9. https://doi.org/10.1053/j.ajkd.2005.10.006 PMid:16377385 DOI: https://doi.org/10.1053/j.ajkd.2005.10.006

Wang H, Wei Y, Kong X, Xu D. Effects of urate-lowering therapy in hyperuricemia on slowing the progression of renal function: A meta-analysis. J Ren Nutr. 2013;23(5):389-96. https://doi.org/10.1053/j.jrn.2012.08.005 PMid:23131573 DOI: https://doi.org/10.1053/j.jrn.2012.08.005

Ito S, Naritomi H, Ogihara T. Impact of serum uric acid on renal function and cardiovascular event in hypertensive patients treated with losartan. Hypertens Res. 2012;35:867-73. https://doi.org/10.1038/hr.2012.59 PMid:22573200 DOI: https://doi.org/10.1038/hr.2012.59

Corry DB, Eslami P, Yamamoto K. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens. 2008;26(2):196-75. https://doi.org/10.1097/HJH.0b013e3282f240bf PMid:18192841 DOI: https://doi.org/10.1097/HJH.0b013e3282f240bf

Perlstein TS, Gumieniak O, Hopkins PN. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int. 2004;66(4):1465-70. https://doi.org/10.1111/j.1523-1755.2004.00909.x PMid:15458439 DOI: https://doi.org/10.1111/j.1523-1755.2004.00909.x

Schumacher HR, Becker MA, Wortmann RL. Effect of febuxostat versus allopurinol and placebo in reducing urate in subjects with hyperuricemia and gout: A 28-week, Phase III, randomised, double-blind, parallel-group trial. Arthritis Rheum. 2008;59(11):1540-48. https://doi.org/10.1002/art.24209 PMid:18975369 DOI: https://doi.org/10.1002/art.24209

Miao Y, Ottenbros SA, Laverman GD. Effect of a reduction in uric acid on renal outcomes during losartan treatment: A post hoc analysis of the reduction of endpoints in non-insulin dependent diabetes mellitus with the angiotensin II antagonist losartan trial. Hypertension. 2011;58(1):2-7. https://doi.org/10.1161/HYPERTENSIONAHA.111.171488 PMid:21632472 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.111.171488