Current Rheumatology Reports

, Volume 12, Issue 2, pp 108–117 | Cite as

Uric Acid and Hypertension: Cause or Effect?

  • Marilda Mazzali
  • Mehmet Kanbay
  • Mark S. Segal
  • Mohamed Shafiu
  • Diana Jalal
  • Daniel I. Feig
  • Richard J. JohnsonEmail author


Uric acid was first associated with primary hypertension in 1874, yet its role in this condition remains unclear. Historically, uric acid was thought to be a secondary response to hypertension or its associated conditions. However, more recent experimental and clinical studies suggest that uric acid could have a contributory role in the pathogenesis of elevated blood pressure. More studies are needed to help dissect the potential mechanisms by which uric acid could initiate this response. It remains possible that uric acid is a marker for xanthine oxidase–associated oxidants and that the latter could be driving the hypertensive response. However, the weight of the evidence suggests that uric acid is a true modifying and possibly causal factor for human primary hypertension. Hence, early management of hyperuricemia might delay the development of essential hypertension.


Xanthine oxidoreductase Allopurinol Blood pressure Hyperuricemia 



Dr. Mazzali and Dr. Johnson have patent applications related to lowering uric acid as a means to prevent or treat hypertension. No other potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bright R: Tabular view of the morbid appearances in 100 cases connected with albuminous urine. Guys Hosp Rep 1836, 1:338–379.Google Scholar
  2. 2.
    Johnson G: On the Diseases of the Kidney. London: John W. Parker and Son; 1852.Google Scholar
  3. 3.
    Gull W, Sutton H: On the pathology of the morbid state commonly called chronic brights disease with contracted kidney ‘arterio-capillary fibrosis.’ Med Chir Trans 1872, 55:325–371.Google Scholar
  4. 4.
    Mahomed FA: The etiology of Bright’s disease and the prealbuminuric state. Med Chir Trans 1874, 39:197–228.Google Scholar
  5. 5.
    Mahomed FA: On chronic Bright’s disease, and its essential symptoms. Lancet 1879, I:398–404.Google Scholar
  6. 6.
    Haig A: The connecting link between the high tension pulse and albuminuria. Br Med J 1890, 1:65–68.PubMedGoogle Scholar
  7. 7.
    Haig A: Uric Acid as a Factor in the Causation of Disease: A Contribution to the Pathology of High Arterial Tension, Headache, Epilepsy, Mental Depression, Gout, Rheumatism, Diabetes, Bright’s Disease, and Other Disorders, edn 1. London: J & A Churchill; 1892. Google Scholar
  8. 8.
    Davis NC: The cardiovascular and renal relations and manifestations of gout. JAMA 1897, 29:261–262.Google Scholar
  9. 9.
    Huchard H: Arteriolosclerosis: including its cardiac form. JAMA 1909, 53:1129.Google Scholar
  10. 10.
    Desgrez A: Influence de la constitution des corps puriques sure leur action vis-a vis de la pression arterielle [in French]. Comptes Rendus de l’Academie des Sciences 1913, 156:93–94.Google Scholar
  11. 11.
    Duckworth D: A Treatise on Gout. London: C. Griffin & Co; 1889.Google Scholar
  12. 12.
    Hood P: A Treatise on Gout, Rheumatism and the Allied Affections. London: J & A. Churchill; 1871.Google Scholar
  13. 13.
    Williams JL: The total nonprotein nitrogen constituents of the blood in arterial hypertension. Arch Int Med 1921, 27:748–754.Google Scholar
  14. 14.
    Fishberg AM: The interpretation of increased blood uric acid in hypertension. Arch Intern Med 1924, 34:503–507.Google Scholar
  15. 15.
    Kylin E: [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome.] Zentralblatt Fur Innere Medizin 1923, 44:105–127.Google Scholar
  16. 16.
    Hitzenberger K, Richter-Quittner M: Ein Beitrag zum Stoffwechsel bei der vaskula¨ren Hypertonie. Wiener Arch Innere Med 1921, 2:189–216.Google Scholar
  17. 17.
    Stanton JR, Freis ED: The serum uric acid concentration in essential hypertension. Proc Soc Exp Biol Med 1947, 66:193–194.PubMedGoogle Scholar
  18. 18.
    Gertler MM, Garn SM, Levine SA: Serum uric acid in relation to age and physique in health and in coronary heart disease. Ann Intern Med 1951, 34:1421–1431.PubMedGoogle Scholar
  19. 19.
    Kinsey D, Walther R, Sise HS, et al.: Incidence of hyperuricemia in 400 hypertensive patients. Circulation 1961, 24:972–973.Google Scholar
  20. 20.
    Breckenridge A: Hypertension and hyperuricaemia. Lancet 1966, 1:15–18.PubMedGoogle Scholar
  21. 21.
    Rakic MT, Valkenburg HA, Davidson RT, et al.: Observations on the natural history of hyperuricemia and gout. I. An eighteen year follow-up of nineteen gouty families. Am J Med 1964, 37:862–871.PubMedGoogle Scholar
  22. 22.
    Cannon PJ, Stason WB, Demartini FE, et al.: Hyperuricemia in primary and renal hypertension. N Engl J Med 1966, 275:457–464.PubMedGoogle Scholar
  23. 23.
    Saggiani F, Pilati S, Targher G, et al.: Serum uric acid and related factors in 500 hospitalized subjects. Metabolism 1996, 45:1557–1561.PubMedGoogle Scholar
  24. 24.
    Johnson RJ, Kang DH, Feig D, et al.: Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003, 41:1183–1190.PubMedGoogle Scholar
  25. 25.
    Wallace SL: Gout and hypertension. Arthritis Rheum 1975, 18:721–724.PubMedGoogle Scholar
  26. 26.
    Hochberg MC, Thomas J, Thomas DJ, et al.: Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum 1995, 38:628–632.PubMedGoogle Scholar
  27. 27.
    Johnson RJ, Titte S, Cade JR, et al.: Uric acid, evolution and primitive cultures. Semin Nephrol 2005, 25:3–8.PubMedGoogle Scholar
  28. 28.
    Decker JL, Lane JJ Jr, Reynolds WE: Hyperuricemia in a male Filipino population. Arthritis Rheum 1962, 5:144–155.PubMedGoogle Scholar
  29. 29.
    Steele TH: Control of uric acid excretion. N Engl J Med 1971, 284:1193–1196.PubMedCrossRefGoogle Scholar
  30. 30.
    Friedl HP, Till GO, Trentz O, et al.: Role of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients. Klin Wochenschr 1991, 69:1109–1112.PubMedGoogle Scholar
  31. 31.
    Facchini F, Chen YD, Hollenbeck CB, et al.: Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA 1991, 266:3008–3011.PubMedGoogle Scholar
  32. 32.
    Quinones GA, Natali A, Baldi S, et al.: Effect of insulin on uric acid excretion in humans. Am J Physiol 1995, 268:E1–E5.Google Scholar
  33. 33.
    DeFronzo RA: The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 1981, 21:165–171.PubMedGoogle Scholar
  34. 34.
    Cappuccio FP, Iacone R, Strazzullo P: Serum uric acid and proximal sodium excretion: an independent association in man (the Olivetti study). J Hypertens Suppl 1991, 9:S280–S281.PubMedGoogle Scholar
  35. 35.
    Cappuccio FP, Strazzullo P, Farinaro E, et al.: Uric acid metabolism and tubular sodium handling. Results from a population-based study. JAMA 1993, 270:354–359.PubMedGoogle Scholar
  36. 36.
    Ramsay LE: Hyperuricaemia in hypertension: role of alcohol. Br Med J 1979, 1:653–654.PubMedGoogle Scholar
  37. 37.
    Messerli FH, Frohlich ED, Dreslinski GR, et al.: Serum uric acid in essential hypertension: an indicator of renal vascular involvement. Ann Intern Med 1980, 93:817–821.PubMedGoogle Scholar
  38. 38.
    Leyva F, Anker S, Swan JW, et al.: Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 1997, 18:858–865.PubMedGoogle Scholar
  39. 39.
    Ruilope LM, Rodicio JL: Renal surrogates in essential hypertension. Clin Exp Hypertens 1999, 21:609–614.PubMedGoogle Scholar
  40. 40.
    Ames BN, Cathcart R, Schwiers E, et al.: Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 1981, 78:6858–6862.PubMedGoogle Scholar
  41. 41.
    Proctor P: Similar functions of uric acid and ascorbate in man? Nature 1970, 228:868.PubMedGoogle Scholar
  42. 42.
    Reyes AJ, Leary WP: The increase in serum uric acid induced by diuretics could be beneficial to cardiovascular prognosis in hypertension: a hypothesis. J Hypertens 2003, 21:1775–1777.PubMedGoogle Scholar
  43. 43.
    Waring WS, McKnight JA, Webb DJ, et al.: Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers. Diabetes 2006, 55:3127–3132.PubMedGoogle Scholar
  44. 44.
    Waring WS, Webb DJ, Maxwell SR: Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 2001, 38:365–371.PubMedGoogle Scholar
  45. 45.
    Kuzkaya N, Weissmann N, Harrison DG, et al.: Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: implications for uncoupling endothelial nitric oxide synthase. Biochem Pharmacol 2005, 70:343–354.PubMedGoogle Scholar
  46. 46.
    Nieto FJ, Iribarren C, Gross MD, et al.: Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis 2000, 148:131–139.PubMedGoogle Scholar
  47. 47.
    Vaccarino V, Krumholz HM: Risk factors for cardiovascular disease: one down, many more to evaluate. Ann Intern Med 1999, 131:62–63.PubMedGoogle Scholar
  48. 48.
    Culleton BF, Larson MG, Kannel WB, et al.: Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med 1999, 131:7–13.PubMedGoogle Scholar
  49. 49.
    Izzo JL, Sica DA, Black HR, eds: Hypertension Primer. The Essentials of High Blood Pressure, edn 4. Philadelphia, PA: Wolters Kluwer and Lippincott Williams & Wilkins; 2008.Google Scholar
  50. 50.
    Mellen PB, Bleyer AJ, Erlinger TP, et al.: Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension 2006, 48:1037–1042.PubMedGoogle Scholar
  51. 51.
    Perlstein TS, Gumieniak O, Williams GH, et al.: Uric acid and the development of hypertension: the normative aging study. Hypertension 2006, 48:1031–1036.PubMedGoogle Scholar
  52. 52.
    Selby JV, Friedman GD, Quesenberry CP Jr: Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol 1990, 131:1017–1027.PubMedGoogle Scholar
  53. 53.
    Sundstrom J, Sullivan L, D’Agostino RB, et al.: Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005, 45:28–33.PubMedGoogle Scholar
  54. 54.
    Masuo K, Kawaguchi H, Mikami H, et al.: Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003, 42:474–480.PubMedGoogle Scholar
  55. 55.
    Dyer AR, Liu K, Walsh M, et al.: Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults. J Hum Hypertens 1999, 13:13–21.PubMedGoogle Scholar
  56. 56.
    Alper AB Jr, Chen W, Yau L, et al.: Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension 2005, 45:34–38.PubMedGoogle Scholar
  57. 57.
    Imazu M, Yamamoto H, Toyofuku M, et al.: Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study. Hypertens Res 2001, 24:531–536.PubMedGoogle Scholar
  58. 58.
    Krishnan E, Kwoh CK, Schumacher HR, et al.: Hyperuricemia and incidence of hypertension among men without metabolic syndrome. Hypertension 2007, 49:298–303.PubMedGoogle Scholar
  59. 59.
    Nagahama K, Inoue T, Iseki K, et al.: Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res 2004, 27:835–841.PubMedGoogle Scholar
  60. 60.
    Nakanishi N, Okamoto M, Yoshida H, et al.: Serum uric acid and risk for development of hypertension and impaired fasting glucose or type II diabetes in Japanese male office workers. Eur J Epidemiol 2003, 18:523–530.PubMedGoogle Scholar
  61. 61.
    Jossa F, Farinaro E, Panico S, et al.: Serum uric acid and hypertension: the Olivetti heart study. J Hum Hypertens 1994, 8:677–681.PubMedGoogle Scholar
  62. 62.
    Zhang W, Sun K, Yang Y, et al.: Plasma uric acid and hypertension in a Chinese community: prospective study and metaanalysis. Clin Chemistry 2009, 55:2026–2034.Google Scholar
  63. 63.
    Forman JP, Choi H, Curhan GC: Uric acid and insulin sensitivity and risk of incident hypertension. Arch Intern Med 2009, 169:155–162.PubMedGoogle Scholar
  64. 64.
    Hunt SC, Stephenson SH, Hopkins PN, et al.: Predictors of an increased risk of future hypertension in Utah. A screening analysis. Hypertension 1991, 17:969–976.PubMedGoogle Scholar
  65. 65.
    Forman JP, Choi H, Curhan GC: Plasma uric acid level and risk for incident hypertension among men. J Am Soc Nephrol 2007, 18:287–292.PubMedGoogle Scholar
  66. 66.
    Mazzali M, Hughes J, Kim YG, et al.: Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001, 38:1101–1106.PubMedGoogle Scholar
  67. 67.
    Sanchez-Lozada LG, Tapia E, Soto V, et al.: Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia. Nephrol Dial Transplant 2007, 23:1179–1185.PubMedGoogle Scholar
  68. 68.
    Sanchez-Lozada LG, Tapia E, Avila-Casado C, et al.: Mild hyperuricemia induces glomerular hypertension in normal rats. Am J Physiol 2002, 283:F1105–F1110.Google Scholar
  69. 69.
    Sanchez-Lozada LG, Tapia E, Santamaria J, et al.: Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005, 67:237–247.PubMedGoogle Scholar
  70. 70.
    Khosla UM, Zharikov S, Finch JL, et al.: Hyperuricemia induces endothelial dysfunction. Kidney Int 2005, 67:1739–1742.PubMedGoogle Scholar
  71. 71.
    Mazzali M, Kanellis J, Han L, et al.: Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol 2002, 282:F991–F997.Google Scholar
  72. 72.
    Sanchez-Lozada LG, Soto V, Tapia E, et al.: Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol 2008, 95:F1134–F1141.Google Scholar
  73. 73.
    Sanchez-Lozada LG, Tapia E, Lopez-Molina R, et al.: Effects of acute and chronic L-arginine treatment in experimental hyperuricemia. Am J Physiol 2007, 292:F1238–F1244.Google Scholar
  74. 74.
    Corry DB, Eslami P, Yamamoto K, et al.: Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008, 26:269–275.PubMedGoogle Scholar
  75. 75.
    • Sautin YY, Nakagawa T, Zharikov S, et al.: Adverse effects of the classical antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 2007, 293:C584–C596. This was the first key study to show uric acid is a pro-oxidant within the cell.PubMedGoogle Scholar
  76. 76.
    Gersch C, Palii SP, Imaram W, et al.: Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. Nucleosides Nucleotides Nucleic Acids 2009, 28:118–149.PubMedGoogle Scholar
  77. 77.
    Santos CX, Anjos EI, Augusto O: Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation. Arch Biochem Biophys 1999, 372:285–294.PubMedGoogle Scholar
  78. 78.
    Gersch C, Palii SP, Kim KM, et al.: Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 2008, 27:967–978.PubMedGoogle Scholar
  79. 79.
    Watanabe S, Kang DH, Feng L, et al.: Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension 2002, 40:355–360.PubMedGoogle Scholar
  80. 80.
    Rao GN, Corson MA, Berk BC: Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem 1991, 266:8604–8608.PubMedGoogle Scholar
  81. 81.
    Kang DH, Han L, Ouyang X, et al.: Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol 2005, 25:425–433.PubMedGoogle Scholar
  82. 82.
    Kang DH, Nakagawa T, Feng L, et al.: A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002, 13:2888–2897.PubMedGoogle Scholar
  83. 83.
    Kang DH, Park SK, Lee IK, et al.: Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol 2005, 16:3553–3562.PubMedGoogle Scholar
  84. 84.
    Chao HH, Liu JC, Lin JW, et al.: Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. Acta Pharmacol Sin 2008, 29:1301–1312.PubMedGoogle Scholar
  85. 85.
    Kanellis J, Watanabe S, Li JH, et al.: Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003, 41:1287–1293.PubMedGoogle Scholar
  86. 86.
    Zharikov S, Krotova K, Hu H, et al.: Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol 2008, 295:C1183–C1190.PubMedGoogle Scholar
  87. 87.
    Johnson RJ, Rodriguez-Iturbe B, Kang DH, et al.: A unifying pathway for essential hypertension. Am J Hypertens 2005, 18:431–440.PubMedGoogle Scholar
  88. 88.
    Feig DI, Johnson RJ: Hyperuricemia in childhood primary hypertension. Hypertension 2003, 42:247–252.PubMedGoogle Scholar
  89. 89.
    Feig DI, Nakagawa T, Karumanchi SA, et al.: Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int 2004, 66:281–287.PubMedGoogle Scholar
  90. 90.
    •• Feig DI, Soletsky B, Johnson RJ: Effect of allopurinol on the blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 2008, 300:922–930. This was the first placebo-controlled trial to show an effect of lowering uric acid on hypertension.Google Scholar
  91. 91.
    • Kanbay M, Ozkara A, Selcoki Y, et al.: Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal functions. Int Urol Nephrol 2007, 39:1227–1233. This was one of the first articles to show the potential effect of lowering uric acid on blood pressure.PubMedGoogle Scholar
  92. 92.
    Siu YP, Leung KT, Tong MK, et al.: Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006, 47:51–59.PubMedGoogle Scholar
  93. 93.
    Talaat KM, El-Sheikh AR: The effect of mild hyperuricemia on urinary transforming growth factor beta and the progression of chronic kidney disease. Am J Nephrol 2007, 27:435–440.PubMedGoogle Scholar
  94. 94.
    • Johnson RJ, Perez-Pozo SE, Sautin YY, et al.: Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev 2009, 30:96–116. This is an overview of uric acid and its potential role in insulin resistance and diabetes.PubMedGoogle Scholar
  95. 95.
    Jalal D, Smits G, Johnson RJ, et al.: Increased fructose intake from added sugars is independently associated with elevated blood pressure. Findings from the National Health and Nutrition Examination Survey (2003–2006). J Am Soc Nephrol 2010 (in press).Google Scholar
  96. 96.
    Nguyen S, Choi HK, Lustig RH, et al.: Sugar-sweetened beverages, serum uric acid, and blood pressure in adolescents. J Pediatr 2009, 154:807–813.PubMedGoogle Scholar
  97. 97.
    Forman JP, Choi H, Curhan GC: Fructose and vitamin C intake do not influence risk for developing hypertension. J Am Soc Nephrol 2009, 20:863–871.PubMedGoogle Scholar
  98. 98.
    Dhingra R, Sullivan L, Jacques PF, et al.: Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 2007, 116:480–488.PubMedGoogle Scholar
  99. 99.
    • Perez-Pozo SE, Schold J, Nakagawa T, et al.: Excessive fructose intake induces features of metabolic syndrome in healthy adult males: role of uric acid in the hypertensive response. Int J Obes (Lond) 2009 Dec 22 (Epub ahead of print). Allopurinol blocks fructose-induced elevation of blood pressure in humans.Google Scholar
  100. 100.
    • Feig DI, Kang DH, Johnson RJ: Uric acid and cardiovascular risk. N Engl J Med 2008, 359:1811–1821. This is an overview of the role of uric acid in cardiovascular disease.PubMedGoogle Scholar
  101. 101.
    George J, Carr E, Davies J, et al.: High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation 2006, 114:2508–2516.PubMedGoogle Scholar
  102. 102.
    Caulfield MJ, Munroe PB, O’Neill D, et al.: SLC2A9 is a high-capacity urate transporter in humans. PLoS Med 2008, 5:e197.PubMedGoogle Scholar
  103. 103.
    Bibert S, Hess SK, Firsov D, et al.: Mouse GLUT9: evidences for a urate uniporter. Am J Physiol 2009, 297:F612–F619.CrossRefGoogle Scholar
  104. 104.
    Chaves FJ, Corella D, Blesa S, et al.: Xanthine oxidoreductase polymorphisms: influence in blood pressure and oxidative stress levels. Pharmacogenet Genom 2007, 17:589–596.Google Scholar
  105. 105.
    Yang J, Kamide K, Kokubo Y, et al.: Associations of hypertension and its complications with variations in the xanthine dehydrogenase gene. Hypertens Res 2008, 31:931–940.PubMedGoogle Scholar
  106. 106.
    Franse LV, Pahor M, Di Bari M, et al.: Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP). J Hypertens 2000, 18:1149–1154.PubMedGoogle Scholar
  107. 107.
    Langford HG, Blaufox MD, Borhani NO, et al.: Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program. Arch Intern Med 1987, 147:645–649.PubMedGoogle Scholar
  108. 108.
    Reungjui S, Roncal CA, Mu W, et al.: Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J Am Soc Nephrol 2007, 18:2724–2731.PubMedGoogle Scholar
  109. 109.
    Sautin YY, Johnson RJ: Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008, 27:608–619.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Marilda Mazzali
    • 1
  • Mehmet Kanbay
    • 1
  • Mark S. Segal
    • 1
  • Mohamed Shafiu
    • 1
  • Diana Jalal
    • 1
  • Daniel I. Feig
    • 1
  • Richard J. Johnson
    • 1
    Email author
  1. 1.Division of Renal Diseases and Hypertension, Mail Stop C281University of Colorado DenverAuroraUSA

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