Uric Acid in the Pathogenesis of Hypertension

  • Daniel I. FeigEmail author
Reference work entry


Over the last century uric acid has been considered a possible risk factor for hypertension, cardiovascular disease, and kidney disease. Only in the last 15 years, however, have there been animal models and clinical trials to support a truly mechanistic link. Results from animal models suggest a two-phase mechanism for the development of hyperuricemic hypertension, in which uric acid induces acute vasoconstriction by activation of the renin-angiotensin system, followed by enhanced uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis. The acute phase of hypertension in that model remains uric acid dependent and sodium independent, whereas the chronic hypertension in experimental models becomes uric acid independent and sodium dependent. Small clinical trials, performed in adolescents with newly diagnosed essential hypertension, demonstrate that reduction of plasma uric acid can reduce blood pressure. Small clinical trials in older adults and persons with chronic renal disease have demonstrated less response to urate lowering therapy, consistent with the two-step model. The available data suggest that uric acid, given its apparent role in the pathogenesis of hypertension, may be a viable target for treatment or prevention in some cases of early onset hypertension.


Uric acid Hypertension Fructose Children Obesity Metabolic syndrome Cardiovascular disease Clinical trials 


  1. Alaygut D, Torun-Bayram M, Soylu A et al (2013) Chronic kidney disease in an adolescent with hyperuricemia: familial juvenile hyperuricemic nephropathy. Turk J Pediatr 55:637–640PubMedGoogle Scholar
  2. Alderman MH, Cohen H, Madhavan S et al (1999) Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 34:144–150PubMedGoogle Scholar
  3. Alper AB Jr, Chen W, Yau L et al (2005) Childhood uric acid predicts adult blood pressure: the Bogalusa heart study. Hypertension 45:34–38PubMedGoogle Scholar
  4. Bellomo G, Venanzi S, Verdura C et al (2010) Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis 56:264–272PubMedGoogle Scholar
  5. Bickel C, Rupprecht HJ, Blankenberg S et al (2002) Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease. Am J Cardiol 89:12–17PubMedGoogle Scholar
  6. Borges RL, Hirota AH, Quinto BM et al (2009) Uric acid as a marker for renal dysfunction in hypertensive women on diuretic and nondiuretic therapy. J Clin Hypertens (Greenwich) 11:253–259Google Scholar
  7. Bos MJ, Koudstaal PJ, Hofman A et al (2006) Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke 37:1503–1507PubMedGoogle Scholar
  8. Brand FN, McGee DL, Kannel WB et al (1985) Hyperuricemia as a risk factor of coronary heart disease: the Framingham study. Am J Epidemiol 121:11–18PubMedGoogle Scholar
  9. Brown C, Culloo A, Yepuri G et al (2008) Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol Regul Integr Comp Physiol 294:R730–R737PubMedGoogle Scholar
  10. Cannella AC, Mikuls TR (2005) Understanding treatments for gout. Am J Manag Care 11:S451–S458PubMedGoogle Scholar
  11. Chen N, Wang W, Huang Y et al (2009a) Community-based study on CKD subjects and the associated risk factors. Nephrol Dial Transplant 24:2117–2123PubMedPubMedCentralGoogle Scholar
  12. Chen YC, Su CT, Wang ST et al (2009b) A preliminary investigation of the association between serum uric acid and impaired renal function. Chang Gung Med J 32:66–71PubMedGoogle Scholar
  13. Chen L, Caballero B, Mitchell DC et al (2010) Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: a prospective study among United States adults. Circulation 121:2398–2406PubMedPubMedCentralGoogle Scholar
  14. Chonchol M, Shlipak MG, Katz R et al (2007) Relationship of uric acid with progression of kidney disease. Am J Kidney Dis 50:239–247Google Scholar
  15. Cirillo P, Gersch MS, Mu W et al (2009) Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol 20:545–553PubMedPubMedCentralGoogle Scholar
  16. Culleton BF, Larson MG, Kannel WB et al (1999) Serum uric acid and risk for cardiovascular disease and death: the Framingham heart study. Ann Intern Med 131:7–13PubMedGoogle Scholar
  17. Daskalopoulou SS, Athyros VG, Elisaf M et al (2004) The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int 66:1714–1715PubMedGoogle Scholar
  18. Davis N (1897) The cardiovascular and renal relations and manifestations of gout. JAMA 29:261–262Google Scholar
  19. De Cosmo S, Viazzi F, Pacilli A et al (2015) Serum uric acid and risk of CKD in type 2 diabetes. Clin J Am Soc Nephrol 10:1921–1929PubMedPubMedCentralGoogle Scholar
  20. Desgrez A (1913) Influence de la constitution des corps puriqes sure leur action vis-a vis de la pression arterielle. C R Acad Sci 156:93–94Google Scholar
  21. Dyer AR, Liu K, Walsh M et al (1999) Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults. J Hum Hypertens 13:13–21PubMedGoogle Scholar
  22. Ejaz AA, Kambhampati G, Ejaz NI et al (2012b) Post-operative serum uric acid and acute kidney injury. J Nephrol 25:497–505PubMedGoogle Scholar
  23. Ejaz AA, Dass B, Lingegowda V et al (2013) Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery. Int Urol Nephrol 45(2):449–458 (Epub 2012)PubMedGoogle Scholar
  24. Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and nutrition examination survey. JAMA 283:2404–2410PubMedGoogle Scholar
  25. Feig DI, Johnson RJ (2003) Hyperuricemia in childhood primary hypertension. Hypertension 42:247–252PubMedPubMedCentralGoogle Scholar
  26. Feig DI, Nakagawa T, Karumanchi SA et al (2004) Hypothesis: uric acid, nephron number and the pathogenesis of essential hypertension. Kidney Int 66:281–287PubMedGoogle Scholar
  27. Feig DI, Soletsky B, Johnson RJ (2008) Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 300:924–932PubMedPubMedCentralGoogle Scholar
  28. Fessel WJ, Siegelaub AB, Johnson ES (1973) Correlates and consequences of asymptomatic hyperuricemia. Arch Intern Med 132:44–54PubMedGoogle Scholar
  29. Foley RN, Wang C, Ishani A et al (2007) NHANES III: influence of race on GFR thresholds and detection of metabolic abnormalities. J Am Soc Nephrol 18:2575–2582PubMedGoogle Scholar
  30. Forman JP, Choi H, Curhan GC (2007) Plasma uric acid level and risk for incident hypertension among men. J Am Soc Nephrol 18:287–292PubMedGoogle Scholar
  31. Forman JP, Choi H, Curhan GC (2009) Uric acid and insulin sensitivity and risk of incident hypertension. Arch Intern Med 169:155–162PubMedPubMedCentralGoogle Scholar
  32. Fox IH, Kelley WN (1972) Studies on the mechanism of fructose-induced hyperuricemia in man. Metabolism 21:713–721PubMedGoogle Scholar
  33. Franse LV, Pahor M, Di Bari M et al (2000) Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP). J Hypertens 18:1149–1154PubMedGoogle Scholar
  34. Gersch MS, Mu W, Cirillo P et al (2007) Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am J Physiol Renal Physiol 293:F1256–F1261PubMedGoogle Scholar
  35. Goldstein HS, Manowitz P (1993) Relation between serum uric acid and blood pressure in adolescents. Ann Hum Biol 20:423–431PubMedGoogle Scholar
  36. Graessler J, Graessler A, Unger S et al (2006) Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population. Arthritis Rheum 54:292–300PubMedGoogle Scholar
  37. Grayson PC, Kim SY, LaValley M et al (2011) Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 63:102–110Google Scholar
  38. Gruskin AB (1985) The adolescent with essential hypertension. Am J Kidney Dis 6:86–90PubMedGoogle Scholar
  39. Gunawardhana L, McLean L, Punzi HA et al (2016) Effect of Febuxostat 80 mg once daily compared with placebo on ambulatory blood pressure in subjects with hyperuricemia and hypertension: a phase 2, double-blind, placebo-controlled study. Hypertension (Submitted)Google Scholar
  40. Gutierrez-Macias A, Lizarralde-Palacios E, Martinez-Odriozola P et al (2005) Fatal allopurinol hypersensitivity syndrome after treatment of asymptomatic hyperuricaemia. BMJ 331:623–624PubMedPubMedCentralGoogle Scholar
  41. Haig A (1897) Uric acid as a factor in the causation of disease, 4th edn. J & A Churchill, LondonGoogle Scholar
  42. Hakoda M, Masunari N, Yamada M et al (2005) Serum uric acid concentration as a risk factor for cardiovascular mortality: a longterm cohort study of atomic bomb survivors. J Rheumatol 32:906–912PubMedGoogle Scholar
  43. Hallfrisch J (1990) Metabolic effects of dietary fructose. FASEB J 4:2652–2660PubMedGoogle Scholar
  44. Hosoya T, Kimura K, Itoh S et al (2014) The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study. Trials 15:26PubMedPubMedCentralGoogle Scholar
  45. Huchard H (1909) Arteriolosclerosis: including its cardiac form. JAMA 53:1129Google Scholar
  46. Hunt SC, Stephenson SH, Hopkins PN et al (1991) Predictors of an increased risk of future hypertension in Utah. A screening analysis. Hypertension 17:969–976PubMedGoogle Scholar
  47. Hwang IS, Ho H, Hoffman BB et al (1987) Fructose-induced insulin resistance and hypertension in rats. Hypertension 10:512–516PubMedGoogle Scholar
  48. Hwang LC, Tsai CH, Chen TH (2006) Overweight and obesity-related metabolic disorders in hospital employees. J Formos Med Assoc 105:56–63PubMedGoogle Scholar
  49. Imazu M, Yamamoto H, Toyofuku M et al (2001) Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima study. Hypertens Res 24:531–536PubMedGoogle Scholar
  50. Iseki K, Oshiro S, Tozawa M et al (2001) Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 24:691–697PubMedGoogle Scholar
  51. Jalal DI, Rivard CJ, Johnson RJ et al (2010) Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the coronary artery calcification in type 1 diabetes study. Nephrol Dial Transplant 25:1865–1869PubMedPubMedCentralGoogle Scholar
  52. Johnson RJ, Herrera-Acosta J, Schreiner GF et al (2002) Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med 346:913–923PubMedGoogle Scholar
  53. Johnson RJ, Segal MS, Srinivas T et al (2005) Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol 16:1909–1919PubMedGoogle Scholar
  54. Jolly SE, Mete M, Wang H et al (2012) Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. J Clin Hypertens (Greenwich) 14:71–77Google Scholar
  55. Jones DP, Richey PA, Alpert BS (2009) Comparison of ambulatory blood pressure reference standards in children evaluated for hypertension. Blood Press Monit 14:103–107PubMedPubMedCentralGoogle Scholar
  56. Jossa F, Farinaro E, Panico S et al (1994) Serum uric acid and hypertension: the Olivetti heart study. J Hum Hypertens 8:677–681PubMedGoogle Scholar
  57. Kahn HA, Medalie JH, Neufeld HN et al (1972) The incidence of hypertension and associated factors: the Israel ischemic heart study. Am Heart J 84:171–182PubMedGoogle Scholar
  58. Kanbay M, Ozkara A, Selcoki Y et al (2007) Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol 39:1227–1233PubMedGoogle Scholar
  59. Kanellis J, Watanabe S, Li JH et al (2003) Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 41:1287–1293PubMedGoogle Scholar
  60. Kang DH, Johnson RJ (2003) Uric acid induces C-reactive protein expression via upregulation of angiotensin type I receptor in vascular endothelial and smooth muscle cells. J Am Soc Nephrol 14:136A. F-PO336Google Scholar
  61. Kang DH, Nakagawa T, Feng L et al (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13:2888–2897PubMedGoogle Scholar
  62. Kang DH, Han L, Ouyang X et al (2005) Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol 25:425–433PubMedGoogle Scholar
  63. Krishnan E, Kwoh CK, Schumacher HR et al (2007) Hyperuricemia and incidence of hypertension among men without metabolic syndrome. Hypertension 49:298–303PubMedGoogle Scholar
  64. Kupferman J, Amador JJ, Lynch KE et al (2016) Characterization of mesoamerican nephropathy in a kidney failure hotspot in Nicaragua. Am J Kidney Dis 68:716PubMedGoogle Scholar
  65. Lebensberger JD, Howard TH, Muntner P et al (2016) Identifying risk factors for sickle cell nephropathy: a cross-sectional study. Pediatr Nephrol 31(8):1363–1368. PMID: 27011218Google Scholar
  66. Lee JE, Kim YG, Choi YH et al (2006) Serum uric acid is associated with microalbuminuria in prehypertension. Hypertension 47:962–967PubMedGoogle Scholar
  67. Lehto S, Niskanen L, Ronnemaa T et al (1998) Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke 29:635–639PubMedGoogle Scholar
  68. Leite ML (2011) Uric acid and fibrinogen: age-modulated relationships with blood pressure components. J Hum Hypertens 25:476–483PubMedGoogle Scholar
  69. Li L, Yang C, Zhao Y et al (2014) Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: a systematic review and meta-analysis based on observational cohort studies. BMC Nephrol 15:122PubMedPubMedCentralGoogle Scholar
  70. Liese AD, Hense HW, Lowel H et al (1999) Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases. Epidemiology 10:391–397PubMedGoogle Scholar
  71. Loeffler LF, Navas-Acien A, Brady TM et al (2012) Uric acid level and elevated blood pressure in US adolescents: National Health and nutrition examination survey, 1999–2006. Hypertension 59:811–817PubMedPubMedCentralGoogle Scholar
  72. Maahs DM, Caramori L, Cherney DZ et al (2013) Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study. Curr Diab Rep 13:550–559PubMedPubMedCentralGoogle Scholar
  73. Madero M, Sarnak MJ, Wang X et al (2009) Uric acid and long-term outcomes in CKD. Am J Kidney Dis 53:796–803PubMedPubMedCentralGoogle Scholar
  74. Mahomed FA (1879) On chronic Bright’s disease, and its essential symptoms. Lancet 1:399–401Google Scholar
  75. Masseoud D, Rott K, Liu-Bryan R et al (2005) Overview of hyperuricaemia and gout. Curr Pharm Des 11:4117–4124PubMedGoogle Scholar
  76. Masuo K, Kawaguchi H, Mikami H et al (2003) Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 42:474–480PubMedGoogle Scholar
  77. Mazza A, Pessina AC, Pavei A et al (2001) Predictors of stroke mortality in elderly people from the general population. The cardiovascular study in the elderly. Eur J Epidemiol 17:1097–1104PubMedGoogle Scholar
  78. Mazzali M, Hughes J, Kim YG et al (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106PubMedGoogle Scholar
  79. Mazzali M, Kanellis J, Han L et al (2002) Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol 282:F991–F997PubMedGoogle Scholar
  80. McArdle PF, Parsa A, Chang YP et al (2008) Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish. Arthritis Rheum 58:2874–2881PubMedPubMedCentralGoogle Scholar
  81. McMullen CJ, Borgi L, Curhan G et al (2015) Effect of uric acid lowering on ambulatory blood pressure: a randomized, double-blind, placebo-controlled clinical trial. American Society of Nephrology, Annual Meeting 2015: FR-OR046Google Scholar
  82. Mellen PB, Bleyer AJ, Erlinger TP et al (2006) Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension 48:1037–1042PubMedGoogle Scholar
  83. Moriarity JT, Folsom AR, Iribarren C et al (2000) Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) study. Ann Epidemiol 10:136–143PubMedGoogle Scholar
  84. Nagahama K, Inoue T, Iseki K et al (2004) Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res 27:835–841PubMedGoogle Scholar
  85. Nakagawa T, Hu H, Zharikov S et al (2006) A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 290:F625–F631PubMedGoogle Scholar
  86. Nakanishi N, Okamato M, Yoshida H et al (2003) Serum uric acid and the risk for development of hypertension and imparied fasting glucose or type II diabetes in Japanese male office workers. Eur J Epidemiol 18:523–530PubMedGoogle Scholar
  87. Nefzger MD, Acheson RM, Heyman A (1973) Mortality from stroke among U.S. veterans in Georgia and 5 western states. I. Study plan and death rates. J Chronic Dis 26:393–404PubMedGoogle Scholar
  88. Nguyen S, Choi H, Lustig R et al (2009) The association of sugar sweetened beverage consumption on serum uric acid and blood pressure in a nationally representative sample of adolescents. J Pediatr 154:807–813PubMedPubMedCentralGoogle Scholar
  89. Niskanen LK, Laaksonen DE, Nyyssonen K et al (2004) Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 164:1546–1551PubMedGoogle Scholar
  90. Noone DG, Marks SD (2013) Hyperuricemia is associated with hypertension, obesity, and albuminuria in children with chronic kidney disease. J Pediatr 162(1):128–132PubMedGoogle Scholar
  91. Obermayr RP, Temml C, Gutjahr G et al (2008) Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol 19:2407–2413PubMedPubMedCentralGoogle Scholar
  92. Park JT, Kim DK, Chang TI et al (2009) Uric acid is associated with the rate of residual renal function decline in peritoneal dialysis patients. Nephrol Dial Transplant 24:3520–3525PubMedGoogle Scholar
  93. Parsa A, Brown E, Weir MR et al (2012) Genotype-based changes in serum uric acid affect blood pressure. Kidney Int 81:502–507PubMedGoogle Scholar
  94. Perez-Pozo SE, Schold J, Nakagawa T et al (2009) Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond) 34:454–461Google Scholar
  95. Perlstein TS, Gumieniak O, Williams GH et al (2006) Uric acid and the development of hypertension: the normative aging study. Hypertension 48:1031–1036PubMedGoogle Scholar
  96. Price K, Sautin Y, Long D et al (2006) Human vascular smooth muscle cells express a urate transporter. J Am Soc Nephrol 17:1791–1795PubMedGoogle Scholar
  97. Reyes AJ (2005) The increase in serum uric acid concentration caused by diuretics might be beneficial in heart failure. Eur J Heart Fail 7:461–467PubMedGoogle Scholar
  98. Rodenbach KE, Schneider MF, Furth SL et al (2015) Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. Am J Kidney Dis 66:984–992PubMedPubMedCentralGoogle Scholar
  99. Rodriguez-Iturbe B, Vaziri ND, Herrera-Acosta J et al (2004) Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all. Am J Physiol Renal Physiol 286:F606–F616PubMedGoogle Scholar
  100. Roncal-Jimenez C, Garcia-Trabanino R, Barregard L et al (2016) Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on mesoamerican nephropathy. Am J Kidney Dis 67:20–30PubMedGoogle Scholar
  101. Roncal CA, Mu W, Croker B et al (2007) Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Am J Physiol Renal Physiol 292:F116–F122PubMedGoogle Scholar
  102. Rovda Iu I (1992) Uric acid and arterial hypertension. Pediatriia 10–12:74–78Google Scholar
  103. Rovda Iu I, Kazakova LM, Plaksina EA (1990) Parameters of uric acid metabolism in healthy children and in patients with arterial hypertension. Pediatriia 8:19–22Google Scholar
  104. Saito I, Folsom AR, Brancati FL et al (2000) Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study. Ann Intern Med 133:81–91PubMedGoogle Scholar
  105. Sakata K, Hashimoto T, Ueshima H et al (2001) Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980–1994. National Integrated Projects for prospective observation of non-communicable diseases and its trend in the aged. Eur J Epidemiol 17:461–468PubMedGoogle Scholar
  106. Sanchez-Lozada LG, Tapia E, Lopez-Molina R et al (2007) Effects of acute and chronic l-arginine treatment in experimental hyperuricemia. Am J Physiol Renal Physiol 292:F1238–F1244PubMedGoogle Scholar
  107. Sautin YY, Nakagawa T, Zharikov S et al (2007) Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 293:C584–C596PubMedGoogle Scholar
  108. Schlesinger N (2005) Dietary factors and hyperuricaemia. Curr Pharm Des 11:4133–4138PubMedGoogle Scholar
  109. See LC, Kuo CF, Chuang FH et al (2009) Serum uric acid is independently associated with metabolic syndrome in subjects with and without a low estimated glomerular filtration rate. J Rheumatol 36:1691–1698PubMedGoogle Scholar
  110. Selby JV, Friedman GD, Quesenberry CP Jr (1990) Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol 131:1017–1027PubMedGoogle Scholar
  111. Shankar A, Klein R, Klein BE et al (2006) The association between serum uric acid level and long-term incidence of hypertension: population-based cohort study. J Hum Hypertens 20:937–945PubMedGoogle Scholar
  112. Silverstein DM, Srivaths PR, Mattison P et al (2011) Serum uric acid is associated with high blood pressure in pediatric hemodialysis patients. Pediatr Nephrol 26:1123–1128PubMedGoogle Scholar
  113. Simon JA (2006) Clinical trials of uric acid lowering for coronary heart disease risk reduction. Am J Med 119:e5; author reply e7PubMedGoogle Scholar
  114. Simon JA, Lin F, Vittinghoff E et al (2006) The relation of postmenopausal hormone therapy to serum uric acid and the risk of coronary heart disease events: the heart and estrogen-progestin replacement study (HERS). Ann Epidemiol 16:138–145PubMedGoogle Scholar
  115. Siu YP, Leung KT, Tong MK et al (2006) Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 47:51–59PubMedGoogle Scholar
  116. Soletsky B, Feig DI (2012) Uric acid reduction rectifies pre-hypertension in obese adolescents. Hypertension 60(5):1148–1156PubMedGoogle Scholar
  117. Spain H, Plumb T, Mikuls TR (2014) Gout as a manifestation of familial juvenile hyperuricemic nephropathy. J Clin Rheumatol 20:442–444PubMedGoogle Scholar
  118. Staessen J (1991) The determinants and prognostic significance of serum uric acid in elderly patients of the European working party on high blood pressure in the elderly trial. Am J Med 90:50S–54SPubMedGoogle Scholar
  119. Sturm G, Kollerits B, Neyer U et al (2008) Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The mild to moderate kidney disease (MMKD) study. Exp Gerontol 43:347–352PubMedGoogle Scholar
  120. Suliman ME, Johnson RJ, Garcia-Lopez E et al (2006) J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis 48:761–771Google Scholar
  121. Sundstrom J, Sullivan L, D’Agostino RB et al (2005) Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 45:28–33PubMedGoogle Scholar
  122. Taniguchi Y, Hayashi T, Tsumura K et al (2001) Serum uric acid and the risk for hypertension and type 2 diabetes in Japanese men. The Osaka Health Survey. J Hypertens 19:1209–1215PubMedGoogle Scholar
  123. Toma I, Kang J, Meer E et al (2007) Uric acid triggers renin release via a macula densa-dependent pathway. In: American Society of Nephrology, Annual Meeting 2007; Renal Week. F-PO240Google Scholar
  124. Török E, Gyarfas I, Csukas M (1985) Factors associated with stable high blood pressure in adolescents. J Hypertens Suppl 3(Suppl 3):S389–S390Google Scholar
  125. Verdecchia P, Schillaci G, Reboldi G et al (2000) Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study. Hypertension 36:1072–1078PubMedGoogle Scholar
  126. Vos MB, Kaar JL, Welsh JA et al (2016) Added sugars and cardiovascular disease risk in children: a scientific statement from the American Heart Association. Circulation. pii: CIR.0000000000000439. [Epub ahead of print] PMID: 27550974Google Scholar
  127. Vylet’al P, Kublova M, Kalbacova M et al (2006) Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome. Kidney Int 70:1155–1169PubMedGoogle Scholar
  128. Wang JG, Staessen JA, Fagard RH et al (2001) Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension. Hypertension 37:1069–1074PubMedGoogle Scholar
  129. Watanabe S, Kang DH, Feng L et al (2002) Uric acid hominoid evolution and the pathogenesis of salt-sensitivity. Hypertension 40:355–360PubMedGoogle Scholar
  130. Weiner DE, Tighiouart H, Elsayed EF et al (2008) Uric acid and incident kidney disease in the community. J Am Soc Nephrol 19:1204–1211PubMedPubMedCentralGoogle Scholar
  131. Weir CJ, Muir SW, Walters MR et al (2003) Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke. Stroke 34:1951–1956PubMedGoogle Scholar
  132. Xia X, Luo Q, Li B et al (2016) Serum uric acid and mortality in chronic kidney disease: a systematic review and meta-analysis. Metabolism 65:1326–1341PubMedGoogle Scholar
  133. Yokoi Y, Kondo T, Okumura N et al (2016) Serum uric acid as a predictor of future hypertension: stratified analysis based on body mass index and age. Prev Med 90:201–206PubMedGoogle Scholar
  134. Zhang W, Sun K, Yang Y et al (2009) Plasma uric acid and hypertension in a Chinese community: prospective study and metaanalysis. Clin Chem 55:2026–2034PubMedGoogle Scholar
  135. Zharikov S, Krotova K, Hu H et al (2008) Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol 295:C1183–C1190PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of Pediatric Nephrology, Hypertension and TransplantationUniversity of AlabamaBirminghamUSA

Section editors and affiliations

  • Julie R. Ingelfinger
    • 1
  1. 1.Pediatric Nephrology UnitMassGeneral Hospital for Children at MGH, Harvard Medical SchoolBostonUSA

Personalised recommendations