Skip to main content

Advertisement

Log in

Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions

International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR) >60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function.

Materials and methods

Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients’ serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment.

Results

A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P < 0.05). However, urine protein excretion remained unchanged (P > 0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P > 0.05).

Conclusion

We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S (2004) Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 44(4):642–650

    Article  PubMed  Google Scholar 

  2. Lehto S, Niskanen L, Ronnemaa T, Laakso M (1998) Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke 29(3):635–639

    PubMed  CAS  Google Scholar 

  3. Brand FN, McGee DL, Kannel WB, Stokes J 3rd, Castelli WP (1985) Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study. Am J Epidemiol 121(1):11–18

    PubMed  CAS  Google Scholar 

  4. Johnson RJ, Kivlighn SD, Kim YG, Suga S, Fogo AB (1999) Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis 33(2):225–234

    PubMed  CAS  Google Scholar 

  5. Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13(12):2888–2897

    Article  PubMed  CAS  Google Scholar 

  6. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41(6):1183–1190

    Article  PubMed  CAS  Google Scholar 

  7. Schmidt MI, Duncan BB, Watson RL et al (1996) A metabolic syndrome in whites and African-Americans. The Atherosclerosis Risk in Communities baseline study. Diabetes Care 19:414–418

    Article  PubMed  CAS  Google Scholar 

  8. Yoo TW, Sung KC, Shin HS et al (2005) Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 69:928–933

    Article  PubMed  CAS  Google Scholar 

  9. Vuorinen-Markkola H, Yki-Jarvinen H (1994) Hyperuricemia and insulin resistance, J Clin Endocrinol Metab 78:25–29

    Article  PubMed  CAS  Google Scholar 

  10. 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 290:625–631

    Article  CAS  Google Scholar 

  11. Farquharson CA, Butler R, Hill A et al (2002) Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 106:221–226

    Article  PubMed  CAS  Google Scholar 

  12. Whelton PK, Perneger TV, He J et al (1996) The role of blood pressure as a risk factor for renal disease: a review of the epidemiologic evidence. J Hum Hypertens 10:683–689

    PubMed  CAS  Google Scholar 

  13. Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS (2006) Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 55(10):1293–1301

    Article  PubMed  CAS  Google Scholar 

  14. Levey A, Greene T, Kusek J, Beck G (2000) A simplified equation to predict glomerular filtration rate from serum creatinine (abstract A0828). J Am Soc Nephrol 11:155A

    Google Scholar 

  15. Johnson RJ, Segal MS, Srinivas T, Ejaz A, Mu W, Roncal C, Sanchez-Lozada LG, Gersch M, Rodriguez-Iturbe B, Kang DH, Acosta JH (2005) Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol 16(7):1909–1919

    Article  PubMed  CAS  Google Scholar 

  16. Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH (1966) Hyperuricemia in primary and renal hypertension. N Engl J Med 275(9):457–464

    Article  PubMed  CAS  Google Scholar 

  17. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38(5):1101–1106

    Article  PubMed  CAS  Google Scholar 

  18. Rao GN, Corson MA, Berk BC (1991) Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem 266(13):8604–8608

    PubMed  CAS  Google Scholar 

  19. Harris RC, Breyer MD (2001) Physiological regulation of cyclooxygenase-2 in the kidney. Am J Physiol Renal Physiol 281(1):F1–F11

    PubMed  CAS  Google Scholar 

  20. Lip GY, Beevers M, Beevers DG (2000) Serum urate is associated with baseline renal dysfunction but not survival or deterioration in renal function in malignant phase hypertension. J Hypertens 18(1):97–101

    Article  PubMed  CAS  Google Scholar 

  21. Iseki K, Oshiro S, Tozawa M, Iseki C, Ikemiya Y, Takishita S (2001) Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 24(6):691–697

    Article  PubMed  CAS  Google Scholar 

  22. Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S (2004) Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 44(4):642–650

    Article  PubMed  Google Scholar 

  23. Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 67(1):237–247

    Article  PubMed  Google Scholar 

  24. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241

    Article  PubMed  CAS  Google Scholar 

  25. Choi HK, Mount DB, Reginato AM (2005) American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med 143(7):499–516

    PubMed  CAS  Google Scholar 

  26. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(6957):516–521

    Article  PubMed  CAS  Google Scholar 

  27. Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Tubulointerstitial damage and progression of renal failure. Kidney Int Suppl (99):S82–S86

  28. Rodriguez-Iturbe B, Johnson RJ (2006) Role of inflammatory cells in the kidney in the induction and maintenance of hypertension. Nephrol Dial Transplant 21(2):260–263

    Article  PubMed  Google Scholar 

  29. Gersch MS, Johnson RJ (2006) Uric acid and the immune response. Nephrol Dial Transplant 21(11):3046–3047

    Article  PubMed  CAS  Google Scholar 

  30. Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, Wamsley A, Sheikh-Hamad D, Lan HY, Feng L, Johnson RJ (2003) Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 41(6):1287–1293

    Article  PubMed  CAS  Google Scholar 

  31. Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2(2):275–281

    Article  PubMed  CAS  Google Scholar 

  32. Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 67(1):237–247

    Article  PubMed  Google Scholar 

  33. Nakagawa T, Mazzali M, Kang DH, Kanellis J, Watanabe S, Sanchez-Lozada LG, Rodriguez-Iturbe B, Herrera-Acosta J, Johnson RJ (2003) Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol 23(1):2–7

    Article  PubMed  Google Scholar 

  34. Siu YP, Leung KT, Tong MK, Kwan TH (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(1):51–59

    Article  PubMed  CAS  Google Scholar 

  35. Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W, Krotova K, Block ER, Prabhakar S, Johnson RJ (2005) Hyperuricemia induces endothelial dysfunction. Kidney Int 67(5):1739–1742

    Article  PubMed  Google Scholar 

  36. Butler R, Morris AD, Belch JJ, Hill A, Struthers AD (2000) Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension 35(3):746–751

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Kanbay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanbay, M., Ozkara, A., Selcoki, Y. et al. Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol 39, 1227–1233 (2007). https://doi.org/10.1007/s11255-007-9253-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-007-9253-3

Keywords

Navigation