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30-05-2014 | Gout | Book Chapter | Article

Physiopathology of gout

Authors: Fernando Pérez-Ruiz, Edwin Castillo

Gout can be defined as the presence of monosodium urate crystals (MSUCs) in tissues. These MSUCs may induce acute inflammation when shed into the synovial fluid or cause aggregate-inducing chronic tissue inflammation.

Literature
  1. Enomoto A, Kimura H, Chairoungdua A, et al. Molecular identification of a renal urate–anion exchanger that regulates blood urate levels. Nature. 2002;417:447-452.
  2. Anzai N, Ichida K, Jutabha P, et al. Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans. J Biol Chem. 2008;283:26834-26838.
  3. Kolz M, Johnson T, Sanna S, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009;5:e1000504.
  4. Ichida K, Matsuo H, Takada T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012;3:764.
  5. Enomoto A, Endou H. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol. 2005;9:195-205.
  6. Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, Herrero-Beites A, Garcia-Erauskin G, Ruiz-Lucea E. Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout. Ann Rheum Dis. 1998;57:545-549.
  7. Witkowska K, Smith KM, Yao SYM, et al. Human SlC2A9a and SlC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses. Am J Physiol Renal Physiol. 2012;303:F527-F539.
  8. Nakanishi T, Ohya K, Shimada S, Anzai N, Tamai I. Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. Nephrol Dial Transplant. 2013;28:603-611.
  9. Matsuo H, Takada T, Ichida K, et al. Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Sci Transl Med. 2009;1:5ra11.
  10. Pascual E, Martínez A, Ordóñez S. Gout: the mechanism of urate crystal nucleation and growth. A hypothesis based in facts. Joint Bone Spine. 2013;80:1-4.
  11. Johnson RJ, Andrews P, Benner SA, Oliver W. Theodore E. Woodward Award: The evolution of obesity: insights from the mid-Miocene. Trans Am Clin Climat Assoc. 2010;121:295-308.
  12. Wortmann RL, Fox IH. Limited value of uric acid to creatinine ratios in estimating uric acid excretion. Ann Intern Med. 1980;93:822-825.
  13. Perez-Ruiz F, Calabozo M, García Erauskin G, Ruibal A, Herrero-Beites AM. Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Rheum. 2002;47:610-613.
  14. Moriwaki Y, Yamamoto T, Takahashi S, Yamakita J, Tsutsumi Z, Hada T. Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout. J Rheumatol. 2001;28:1306-1310.
  15. Simkin PA, Hoover PL, Paxson CS, Wilson WF. Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples. Ann Intern Med. 1979;91:44-47.
  16. Yamamoto T, Moriwaki Y, Takahashi S, et al. A simple method of selecting gout patients for treatment with uricosuric agents, using spot urine and blood samples. J Rheumatol. 2002;29:1937-1941.
  17. Perez-Ruiz F, Herrero-Beites AM. Reply to letter: new standards for uric acid excretion and evidence for an inducible transporter. Arthritis Care Res. 2003;49:736-737.
  18. Kannangara DRW, Ramasamy SN, Indraratna PL, et al. Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients. Arthritis Res Ther. 2012;14:R189.
  19. Gutman AB, Yü TF. Gout, a derangement of purine metabolism. Adv Inter Med. 1952;7:227-302.
  20. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2005;52:283-289.
  21. Martin WJ, Shaw O, Liu x, Steiger S, Harper JL. Monosodium urate monohydrate crystal-recruited non-inflammatory monocytes differentiate into M1-like pro-inflammatory macrophages in a peritoneal murine model of gout. Arthritis Rheum. 2011;63:1322-1332.
  22. Pascual E. Persistence of monosodium urate crystals and low-grade inflammation in synovial fluid of patients with untreated gout. Arthritis Rheum. 1991;34:141-145.
  23. Puig JG, de Miguel E, Castillo MC, López Rocha A, Martínez MA, Torres RJ. Asymptomatic hyperuricemia: impact of ultrasonography. Nucleosides Nucleotides Nucleic Acids. 2008;27: 592-595.
  24. Reginato AM, Olsen BR. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear? Curr Opin Rheumatol. 2009;19:134-145.
  25. Schumacher HR. Pathology of the synovial membrane in gout. Light and electron microscopic studies. Arthritis Rheum. 1975;18:771-782.
  26. Dalbeth N, Pool B, Gamble G, et al. Cellular characterization of the gouty tophus: a quantitative analysis [abstract]. Arthitis Rheum. 2009;60(suppl 10:1948.
  27. So A, Busso N. A magic bullet for gout? Ann Rheum Dis. 2009;68:1517-1519.
  28. Perez-Ruiz F, Martin I, Canteli B. Ultrasonographic measurement of tophi as an outcome measure for chronic gout. J Rheumatol. 2007;34:1888-1893.
  29. Dalbeth N, Clark B, Gregory K, et al. Mechanisms of bone erosions in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis. 2009;68: 1290-1295.
  30. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthitis Care Res (Hoboken). 2010;62:170-180.
  31. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:885-892.
  32. 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;63:3136-3141.
  33. Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54:2688-2696.
  34. Krishnan E. Gout and the risk for incident heart failure and systolic dysfunction. BMJ Open. 2012;2:e000282.
  35. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116:894-900.
  36. Wright SA, Filippucci E, McVeigh C, et al. High resolution ultrasonography of the first metatarsal phalangeal joint in gout: a controlled study. Ann Rheum Dis. 2007;66:859-864.
  37. Chen SY, Chen Cl, Shen Ml. Severity of gouty arthritis is associated with 2-wave myocardial infarction: a large-scale, cross-sectional study. Clin Rheumatol. 2007;26:308-313.
  38. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout [published online ahead of print January 12, 2013]. Ann Rheum Dis. doi:10.1136/annrheumdis-2012-202421.
  39. Pascual E, Castellano JA. Treatment with colchicine decreases white cell counts in synovial fluid of asymptomatic knees that contain monosodium urate crystals. J Rheumatol. 1992;19:600-603.
  40. Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol. 2012;39:1458-1464.