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Hyperuricemia and renal function

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Abstract

Increased serum urate concentration is commonly seen in clinical practice. It does not represent a specific disease, nor is it an indication for therapy. Hyperuricemia can be the consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. In essential hypertension, it has been described in up to one third of patients and is directly related to an increase in renal vascular resistance and inversely correlated with renal plasma flow. In other words, abnormal renal hemodynamics, commonly seen in the initial stages of the disease, account for the increased serum urate concentration. This can be maintained if a decrease in glomerular filtration rate takes place. The increase in uric acid has been shown to be a potent predictor of the development of cardiovascular events and death. In addition, uric acid, particularly when elevated, could represent an independent risk factor. On the other hand, an altered renal function predicts in an independent manner a higher cardiovascular risk. For this reason, the predictive capacity of uric acid could be partly dependent on the fact that hyperuricemia runs in parallel with a deranged renal function.

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References and Recommended Reading

  1. Hall AP, Barry PE, Dawber TR, McNamara PM: Epidemiology of gout and hyperuricemia: a long term population study. Am J Med 1967, 42:27–37.

    Article  PubMed  CAS  Google Scholar 

  2. Zalokar J, Lellouch J, Claude JR: Serum urate and gout in 4663 young male workers. Semin Hôp Paris 1981, 57:664–668.

    CAS  Google Scholar 

  3. Noguera Hernando E: Estudio epidemiológico de hiperuricemia y gota en España. Fase I. Madrid: Saned; 1987:8–19.

    Google Scholar 

  4. Paulus HE, Coutts A, Calabro JJ, Klinenberg JR: Clinical significance of hyperuricemia in routinely screened hospitalized men. JAMA 1970, 211:277–281.

    Article  PubMed  CAS  Google Scholar 

  5. Allen DJ, Milosovich G, Mattock AM: Inhibition of monosodium urate crystal growth. Arthritis Rheum 1965, 8:1123–1133.

    Article  PubMed  CAS  Google Scholar 

  6. Campion EW, Glynn RJ, DeLabry LO: Asymptomatic hyperuricemia. Risks and consequences in the normative aging study. Am J Med 1987, 82:421–426.

    Article  PubMed  CAS  Google Scholar 

  7. Mikkelsen WM, Dodge HJ, Valkenburg H: The distribution of serum uric acid values in a population unselected as to gout or hyperuricemia. Tecumseh, Michigan, 1959–1960. Am J Med 1965, 39:242–251.

    Article  PubMed  CAS  Google Scholar 

  8. Nichols A, Suaith ML, Scott JT: Effect of oestrogen therapy on plasma and urinary levels of uric acid. BMJ 1973, 1:449–451.

    Google Scholar 

  9. Mateos Antón F, García Puig J, Ramos T, et al.: Sex differences in uric acid metabolism in adults: Evidence for a lack of influence of estradiol—17beta (e2) on the renal handling of urate. Metabolism 1986, 35:343–248.

    Article  Google Scholar 

  10. Puig JG, Michán AD, Jiménez ML, et al.: Female gout. Clinical spectrum and uric acid metabolism. Arch Intern Med 1991, 151:726–732.

    Article  PubMed  CAS  Google Scholar 

  11. Levinson DJ, Sorensen LB: Renal handling of uric acid in normal and gouty subjects: evidence for a 4-component system. Ann Rheum Dis 1980, 39:173–179.

    PubMed  CAS  Google Scholar 

  12. García Puig J, Mateos Antón F, Muñoz Sanz A, et al.: Renal handling of uric acid in normal subjects by means of the pyrazinamide and probenecid tests. Nephron 1983, 35:183–186.

    Google Scholar 

  13. Seegmiller JE, Grayzel AI, Laster L, Little L: Uric acid production in gout. J Clin Invest 1961, 40:1304–1314.

    PubMed  CAS  Google Scholar 

  14. Levinson DJ, Becker MA: Clinical gout and the pathogenesis of hyperuricemia. In Arthritis and Allied Conditions. 12th ed. Edited by McCarty DJ, Koopman WJ. Philadelphia: Lea & Febiger; 1993:1773–1805.

    Google Scholar 

  15. García Puig J, Mateos Antón F, López Jiménez M, Conthe Gutiérrez P: Renal handling of uric acid in gout: impaired tubular transport of urate not dependent on serum urate levels. Metabolism 1986, 35:1147–1153.

    Article  Google Scholar 

  16. Emmerson BT: Identification of the causes of persistent hyperuricemia. Lancet 1991, 337:1461–1463.

    Article  PubMed  CAS  Google Scholar 

  17. Breckenridge A: Hypertension and hyperuricaemia. Lancet 1966, 1:15–18.

    Article  PubMed  CAS  Google Scholar 

  18. Cannon PJ, Stason WB, Demartini FE, et al.: Hyperuricemia in primary and renal disease. N Engl J Med 1966, 275:457–464.

    Article  PubMed  CAS  Google Scholar 

  19. Messerli FH, Frohlich ED, Dreslinski GR, et al.: Serum uric acid in essential hypertension: an kindicator of renal vascular involvement. Ann Intern Med 1980, 93:817–821.

    PubMed  CAS  Google Scholar 

  20. Mattei P, Arzilli F, Giovannetti R, et al.: Microalbuminuria and renal haemodynamics in essential hypertension. Eur J Clin Invest 1997, 27:755–760.

    Article  PubMed  CAS  Google Scholar 

  21. Ruilope LM, Campo C, Rodríguez-Artalejo F, et al.: Blood pressure and renal function: therapeutic implications. J Hypertens 1996, 14:1259–1263.

    Article  PubMed  CAS  Google Scholar 

  22. Puig JG, Miranda ME, Mateos FA, et al.: Hereditary nephropathy associated with hyperuricemia and gout. Arch Intern Med 1993, 153:357–365.

    Article  PubMed  CAS  Google Scholar 

  23. García Puig J, Ruilope LM: Uric acid as a cardiovascular risk factor in arterial hypertension. J Hypertens 1999, 17:869–872. This is a review on the possible role of uric acid as an independent cardiovascular risk factor.

    Article  Google Scholar 

  24. Tykarski A: Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion. Nephron 1991, 59:364–368.

    Article  PubMed  CAS  Google Scholar 

  25. Capuccio FP, Strazzullo P, Farinaro E, Trevisan M: Uric acid metabolism and tubular sodium handling. Results from a population-based study. JAMA 1993, 270:354–359.

    Article  Google Scholar 

  26. Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities - the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996, 334:374–381.

    Article  PubMed  CAS  Google Scholar 

  27. Quinones-Galvan A, Ferrannini E: Renal effects of insulin in man. J Nephrol 1997, 10:188–191.

    PubMed  CAS  Google Scholar 

  28. Steele TH: Hyperuricemic nephropathies. Nephron 1999, 81(suppl1):45–49.

    Article  PubMed  CAS  Google Scholar 

  29. Kerkalainen P, Sarlund H, Laakso M: Long-term association of cardiovascular risk factors with impaired insulin secretion and insulin resistance. Metabolism 2000, 49:1247–1254. This article shows the association between hyperuricemia and insulin resistance in essential hypertension. Elevated uric acid is present in the metabolic syndrome that frequently accompanies arterial hypertension.

    Article  Google Scholar 

  30. Reaven GM: Insulin resistance: a chicken that has come to roost. Ann N Y Acad Sci 1999, 892:45–57.

    Article  PubMed  CAS  Google Scholar 

  31. Bonora E, Targher G, Zenere MB, et al.: Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study. Int J Obes 1996, 20:975–980.

    CAS  Google Scholar 

  32. Rathman W, Funkhouser E, Dyer AR, Roseman JM: Relation of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA study. Ann Epidemiol 1998, 8:250–261.

    Article  Google Scholar 

  33. Brand FN, McGee DL, Kannel WB, et al.: Hyperuricemia as a risk factor of coronary heart disease: The Framingham Study. Am J Epidemiol 1985, 121:11–18.

    PubMed  CAS  Google Scholar 

  34. Klein R, Klein BE, Cornni JC, et al.: Serum uric acid. Its relationship to coronary heart disease risk factors and cardiovascular disease, Evans County, Georgia. Arch Intern Med 1973, 132:401–410.

    Article  PubMed  CAS  Google Scholar 

  35. Persky VW, Dyer AR, Idris-Soven E, et al.: Uric acid: a risk factor for coronary heart disease? Circulation 1979, 59:969–977.

    PubMed  CAS  Google Scholar 

  36. Reunanen A, Takkunen H, Knekt P, Aromaa A: Hyperuricemia as a risk factor for cardiovascular mortality. Acta Med Scand (Suppl) 1982, 668:49–59.

    CAS  Google Scholar 

  37. Yano K, Reed DM, McGee DL: Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to biologic and lifestyle characteristics. Am J Epidemiol 1984, 119:653–666.

    PubMed  CAS  Google Scholar 

  38. The Hypertension Detection, and Follow-up Program Cooperative Research Group: Mortality findings for steepedcare and referred-care participants in the Hypertension Detection and Follow-up Program, stratified by other risk factors. Prev Med 1985, 14:312–335.

    Article  Google Scholar 

  39. Abbott RD, Brand FN, Kannel WB, Castelli WP: Gout and coronary heart disease: The Framingham Study. J Clin Epidemiol 1988, 41:237–242.

    Article  PubMed  CAS  Google Scholar 

  40. Levine W, Dyer AR, Shekelle RB, et al.: Serum uric acid and 11.5-year mortality of middle-aged women: findings of the Chicago Heart Association Detection Project in Industry. J Clin Epidemiol 1989, 42:257–267.

    Article  PubMed  CAS  Google Scholar 

  41. Selby JV, Friedman GD, Quesenberry CP: Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol 1990, 131:1017–1027.

    PubMed  CAS  Google Scholar 

  42. Staessen J, for members of the European Working Party on High Blood Pressure in the Elderly: The determinants and prognostic significance of serum uric acid in elderly patients of the the European Working Party on High Blood Pressure in the Elderly trial. Am J Med 1991, 90(suppl 3):50S-54S.

    PubMed  CAS  Google Scholar 

  43. Jossa F, Farinaro E, Panico S, et al.: Serum uric acid and hypertension: the Olivetti Heart Study. J Hum Hypertens 1994, 8:677–681.

    PubMed  CAS  Google Scholar 

  44. Freedman DS, Williamson DF, Gunter EW, Byers T: Relation of serum uric acid to mortality and ischemic heart disease. The NHANES I epidemiologic follow-up study. Am J Epidemiol 1995, 141:637–644.

    PubMed  CAS  Google Scholar 

  45. Iribarren C, Sharp DS, Curb JD, Yano K: High uric acid: a metabolic marker of coronary heart disease among alcohol abstainers? J Clin Epidemiol 1996, 49:673–678.

    Article  PubMed  CAS  Google Scholar 

  46. Wannamethee SG, Shaper AG, Whincup PH: Serum urate and the risk of major coronary heart disease events. Heart 1997, 78:147–153.

    PubMed  CAS  Google Scholar 

  47. Lehto S, Niskanen L, Ronnemaa T, Laakso M: Serum uric acid is a strong predictor of stroke in patients with non-insulindependent diabetes mellitus. Stroke 1998, 29:635–639.

    PubMed  CAS  Google Scholar 

  48. Alderman MH, Cohen H, Madhavan S, Kivlighn S: Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 1999, 34:144–150. Uric acid as a predictor of cardiovascular events and death in essential hypertension.

    PubMed  CAS  Google Scholar 

  49. Culleton BF, Larson MG, Kannel WB, Levy D: Serum uric acid and risk for cardiovascular disease and death: The Framingham Heart Study. Ann Intern Med 1999, 131:7–13.

    PubMed  CAS  Google Scholar 

  50. Franse LV, Pahor M, DiBari 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. Diuretic therapy did not protect from events and death in those patients developing hyperuricemia secondary to diuretic administration.

    Article  PubMed  CAS  Google Scholar 

  51. Fang J, Alderman MH: Serum uric acid and cardiovascular mortality. The NHANES I epidemiologic follow-up study, 1971–1992. JAMA 2000, 283:2404–2410. This study discusses uric acid as a predictor of cardiovascular mortality.

    Article  PubMed  CAS  Google Scholar 

  52. Verdecchia P, Schillaci G, Reboldi GP, et al.: The relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The Piuma Study. Hypertension 2000, 36:1072–1078. This study discusses uric acid as a predictor of cardiovascular events and death in essential hypertension.

    PubMed  CAS  Google Scholar 

  53. Langford HG, Blaufox D, Borhani NO, et al.: Is thiazideproduced uric acid elevation harmful? Analysis of data from the Hypertensiojn Detection and Follow-up Program. Arch Intern Med 1987, 147:645–649.

    Article  PubMed  CAS  Google Scholar 

  54. Beck LH: Requiem for gouty nephropathy. Kidney Int 1986, 30:280–287.

    PubMed  CAS  Google Scholar 

  55. Chapman PT, Yarwood H, Harrison AA, et al.: Endothelial activation in monosodium urate monohydrate crystalinduced inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor alpha and interleukin-1. Arthritis Rheum 1997, 40:955–965.

    Article  PubMed  CAS  Google Scholar 

  56. Pahor M, Elam MB, Garrison RJ, et al.: Emerging noninvasive biochemical measures to predict cardiovascular risk. Arch Intern Med 1999, 159:237–245.

    Article  PubMed  CAS  Google Scholar 

  57. Alcázar J, Ruilope L, Ladrón de Guevara P, et al.: Hiperuricemia e hipertensión arterial esencial. Nefrología 1982, 2:145–149.

    Google Scholar 

  58. Ruilope LM, Lahera V, Rodicio JL, Romero JC: Are renal hemodynamics a key factor in the development and maintenance of arterial hypertension in humans? Hypertension 1994, 23:3–9.

    PubMed  CAS  Google Scholar 

  59. ope LM: Kidney dysfunction, a sensitive predictor of cardiovascular risk. Am J Hypertens 2001, in press.

  60. Shulman NB, Ford CE, Hall WD, et al.: Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the Hypertension Detection and Follow-up Program Cooperative Group. Hypertension 1989, 13(suppl 5):I180-I193.

    Google Scholar 

  61. Ruilope LM, Salvetti A, Jamerson K, et al.: Renal function and intensive lowering of bloodpressure in the hypertensive subjects of the Hypertension Optimal Treatment (HOT) Study. J Am Soc Nephrol 2001, 12:218–225. This study describes the capacity of decreased renal function to predict cardiovascular events and death in essential hypertension.

    PubMed  CAS  Google Scholar 

  62. Brown MJ, Palmer CR, Casteigne A, et al.: Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000, 536:366–372.

    Article  Google Scholar 

  63. Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984, 310:356–360.

    Article  PubMed  CAS  Google Scholar 

  64. Campo C, Ruilope LM, Segura J, et al.: Serum urate as a marker of hypertension severity. J Hypertens 2001, in press.

  65. Cockroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16:31–41.

    Article  Google Scholar 

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  1. Unidad de Hipertensión, Hospital 12 de Octubre, 28041, Madrid, Spain

    Luis Miguel Ruilope MD

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  1. Luis Miguel Ruilope MD
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  2. Juan Garcia-Puig
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Ruilope, L.M., Garcia-Puig, J. Hyperuricemia and renal function. Current Science Inc 3, 197–202 (2001). https://doi.org/10.1007/s11906-001-0038-2

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