Skip to main content
Erschienen in: International Urology and Nephrology 4/2007

01.12.2007 | Original Article

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

verfasst von: Mehmet Kanbay, Adem Ozkara, Yusuf Selcoki, Bunyamin Isik, Faruk Turgut, Nuket Bavbek, Ebru Uz, Ali Akcay, Ramazan Yigitoglu, Adrian Covic

Erschienen in: International Urology and Nephrology | Ausgabe 4/2007

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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):642–650PubMedCrossRef 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):642–650PubMedCrossRef
2.
Zurück zum Zitat 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):635–639PubMed 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):635–639PubMed
3.
Zurück zum Zitat 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):11–18PubMed 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):11–18PubMed
4.
Zurück zum Zitat 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):225–234PubMed 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):225–234PubMed
5.
Zurück zum Zitat 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):2888–2897PubMedCrossRef 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):2888–2897PubMedCrossRef
6.
Zurück zum Zitat 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):1183–1190PubMedCrossRef 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):1183–1190PubMedCrossRef
7.
Zurück zum Zitat 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 19:414–418PubMedCrossRef 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 19:414–418PubMedCrossRef
8.
Zurück zum Zitat Yoo TW, Sung KC, Shin HS et al (2005) Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 69:928–933PubMedCrossRef Yoo TW, Sung KC, Shin HS et al (2005) Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 69:928–933PubMedCrossRef
9.
Zurück zum Zitat Vuorinen-Markkola H, Yki-Jarvinen H (1994) Hyperuricemia and insulin resistance, J Clin Endocrinol Metab 78:25–29PubMedCrossRef Vuorinen-Markkola H, Yki-Jarvinen H (1994) Hyperuricemia and insulin resistance, J Clin Endocrinol Metab 78:25–29PubMedCrossRef
10.
Zurück zum Zitat 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 290:625–631CrossRef 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 290:625–631CrossRef
11.
Zurück zum Zitat Farquharson CA, Butler R, Hill A et al (2002) Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 106:221–226PubMedCrossRef Farquharson CA, Butler R, Hill A et al (2002) Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 106:221–226PubMedCrossRef
12.
Zurück zum Zitat 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 10:683–689PubMed 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 10:683–689PubMed
13.
Zurück zum Zitat 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):1293–1301PubMedCrossRef 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):1293–1301PubMedCrossRef
14.
Zurück zum Zitat 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 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
15.
Zurück zum Zitat 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):1909–1919PubMedCrossRef 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):1909–1919PubMedCrossRef
16.
Zurück zum Zitat Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH (1966) Hyperuricemia in primary and renal hypertension. N Engl J Med 275(9):457–464PubMedCrossRef Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH (1966) Hyperuricemia in primary and renal hypertension. N Engl J Med 275(9):457–464PubMedCrossRef
17.
Zurück zum Zitat 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):1101–1106PubMedCrossRef 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):1101–1106PubMedCrossRef
18.
Zurück zum Zitat 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):8604–8608PubMed 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):8604–8608PubMed
19.
Zurück zum Zitat Harris RC, Breyer MD (2001) Physiological regulation of cyclooxygenase-2 in the kidney. Am J Physiol Renal Physiol 281(1):F1–F11PubMed Harris RC, Breyer MD (2001) Physiological regulation of cyclooxygenase-2 in the kidney. Am J Physiol Renal Physiol 281(1):F1–F11PubMed
20.
Zurück zum Zitat 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):97–101PubMedCrossRef 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):97–101PubMedCrossRef
21.
Zurück zum Zitat 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):691–697PubMedCrossRef 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):691–697PubMedCrossRef
22.
Zurück zum Zitat 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):642–650PubMedCrossRef 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):642–650PubMedCrossRef
23.
Zurück zum Zitat 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):237–247PubMedCrossRef 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):237–247PubMedCrossRef
24.
Zurück zum Zitat Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241PubMedCrossRef Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241PubMedCrossRef
25.
Zurück zum Zitat Choi HK, Mount DB, Reginato AM (2005) American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med 143(7):499–516PubMed Choi HK, Mount DB, Reginato AM (2005) American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med 143(7):499–516PubMed
26.
Zurück zum Zitat Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(6957):516–521PubMedCrossRef Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(6957):516–521PubMedCrossRef
27.
Zurück zum Zitat Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Tubulointerstitial damage and progression of renal failure. Kidney Int Suppl (99):S82–S86 Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Tubulointerstitial damage and progression of renal failure. Kidney Int Suppl (99):S82–S86
28.
Zurück zum Zitat 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):260–263PubMedCrossRef 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):260–263PubMedCrossRef
29.
Zurück zum Zitat Gersch MS, Johnson RJ (2006) Uric acid and the immune response. Nephrol Dial Transplant 21(11):3046–3047PubMedCrossRef Gersch MS, Johnson RJ (2006) Uric acid and the immune response. Nephrol Dial Transplant 21(11):3046–3047PubMedCrossRef
30.
Zurück zum Zitat 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):1287–1293PubMedCrossRef 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):1287–1293PubMedCrossRef
31.
Zurück zum Zitat 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):275–281PubMedCrossRef 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):275–281PubMedCrossRef
32.
Zurück zum Zitat 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):237–247PubMedCrossRef 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):237–247PubMedCrossRef
33.
Zurück zum Zitat 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):2–7PubMedCrossRef 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):2–7PubMedCrossRef
34.
Zurück zum Zitat 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):51–59PubMedCrossRef 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):51–59PubMedCrossRef
35.
Zurück zum Zitat 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):1739–1742PubMedCrossRef 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):1739–1742PubMedCrossRef
36.
Zurück zum Zitat 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):746–751PubMed 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):746–751PubMed
Metadaten
Titel
Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions
verfasst von
Mehmet Kanbay
Adem Ozkara
Yusuf Selcoki
Bunyamin Isik
Faruk Turgut
Nuket Bavbek
Ebru Uz
Ali Akcay
Ramazan Yigitoglu
Adrian Covic
Publikationsdatum
01.12.2007
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 4/2007
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-007-9253-3

Weitere Artikel der Ausgabe 4/2007

International Urology and Nephrology 4/2007 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Ist Fasten vor Koronarinterventionen wirklich nötig?

Wenn Eingriffe wie eine Koronarangiografie oder eine Koronarangioplastie anstehen, wird häufig empfohlen, in den Stunden zuvor nüchtern zu bleiben. Ein französisches Forscherteam hat diese Maßnahme hinterfragt.

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

04.06.2024 Typ-2-Diabetes Nachrichten

Wenn ältere Menschen mit Typ-2-Diabetes Schwierigkeiten beim Beschaffen und Zubereiten von Mahlzeiten haben, geht dies mit einem deutlich gesteigerten Risiko für schwere Hypoglykämien einher.

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

04.06.2024 Levonorgestrel Nachrichten

Unter Frauen, die ein Levonorgestrel-freisetzendes intrauterines System (IUS) verwenden, ist die Brustkrebsrate um 13% erhöht. Dafür kommt es deutlich seltener zu Endometrium-, Zervix- und Ovarialkarzinomen.

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

03.06.2024 Semaglutid Nachrichten

Der GLP-1-Agonist Semaglutid hat in der FLOW-Studie bewiesen, dass sich damit die Progression chronischer Nierenerkrankungen bei Patienten mit Typ-2-Diabetes bremsen lässt. Auch in kardiovaskulärer Hinsicht war die Therapie erfolgreich.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.