Use of Allopurinol in Slowing the Progression of Renal Disease Through Its Ability to Lower Serum Uric Acid Level

Siu, Yui-Pong; Leung, Ken Cham Fai; Tong, M.K.H.; Kwan, Tze-Hoi

doi:10.1053/j.ajkd.2005.10.006

Cited by 719 publications

(612 citation statements)

References 26 publications

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“…Second, there is evidence that uric acid may have a causal role in hypertension, 7 the metabolic syndrome, 29,30 and renal disease. 31,32 Adjusting for blood pressure, the metabolic syndrome, and renal function may, therefore, remove mechanisms by which uric acid may cause hypertension, that is, overadjustment in our multivariable model. It is possible that our age-adjusted risk estimates more accurately reflect the risk for hypertension conferred by hyperuricemia than do our multivariable-adjusted risk estimates.…”

Section: Discussionmentioning

confidence: 99%

Uric Acid and the Development of Hypertension

Perlstein

Gumieniak²,

Williams³

et al. 2006

Hypertension

261

105

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Abstract-Experimental evidence supports a causative role for uric acid in the pathogenesis of hypertension. Prospective studies have variably adjusted for relevant confounders and have been of relatively limited duration. We prospectively examined the relationship between uric acid level and the development of hypertension in the Normative Aging Study, a longitudinal cohort of healthy adult men. Key Words: uric acid Ⅲ hypertension Ⅲ renal function Ⅲ prospective studies Ⅲ aging T he association of hyperuricemia with hypertension has long been recognized. 1 It remains unresolved whether the association of hyperuricemia with hypertension is solely because of underlying renal and metabolic abnormalities. Decreased renal blood flow 2 and decreased tubular secretion of uric acid 3 have been associated with hyperuricemia in hypertension. Hyperinsulinemia secondary to insulin resistance may also contribute to the association of hyperuricemia with hypertension. 4,5 Recent observations in experimental hyperuricemia suggest that uric acid may in fact have a pathogenic role in hypertension. 6 Hyperuricemia induces hypertension in experimental animals that corrects with hypouricemic therapy. 7 Elevated serum uric acid level has been associated with increased risk for developing hypertension. 8 -18 The Normative Aging Study (NAS), a longitudinal study of aging begun in 1963 and with ongoing follow-up, presented a unique opportunity to examine the relationship between serum uric acid level and the development of hypertension. The duration of follow-up, Յ40 years, allowed us to assess the durability of the prospective association of uric acid level with hypertension. The comprehensive data collection allowed adjustment for key potential confounding covariates, such as central adiposity, alcohol intake, metabolic parameters, and, in a subset of study subjects, the serum creatinine level. Previous studies have variably accounted for these confounders. Specifically, some did not adjust for blood pressure, 8,9,17,18 Ն2 elements of the metabolic syndrome, 8 -11,13-15 or alcohol intake, 11,12 and only 1 adjusted for renal function. 13 We, therefore, examined the prospective association of serum uric acid level with the development of hypertension among subjects at risk for the development of hypertension within the NAS cohort, including an analysis of those at risk for the development of hypertension at the time of their first serum creatinine determination. We have included in our multivariable model(s) covariates of the metabolic syndrome, alcohol intake, and renal function. MethodsSubjects were participants in the NAS, a longitudinal study of aging established by the Veterans Administration in 1961. 19 The study cohort consists of 2280 community-dwelling men from the greater Boston area who were 21 to 80 years of age on enrollment. Volunteers were screened at entry according to specific health criteria and were free of known chronic medical conditions at the

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Section: Discussionmentioning

confidence: 99%

Uric Acid and the Development of Hypertension

Perlstein

Gumieniak²,

Williams³

et al. 2006

Hypertension

261

105

View full text Add to dashboard Cite

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“…Studies performed in the 1970s were often confounded by short durations of treatment, ineffective lowering of uric acid level, or complicating attacks of gout. However, more recently, Siu et al randomized 54 asymptomatic hyperuricemic patients with chronic kidney disease to allopurinol (a xanthine oxidase inhibitor) or placebo and reported that allopurinol significantly preserved renal function over the year period of observation [15]. Using a different approach, Talaat and El-Sheikh evaluated the effect of withdrawing allopurinol from 50 subjects with chronic kidney disease and noted a marked exacerbation of blood pressure with renal progression in the subset that was not receiving agents to block the renin angiotensin system [16].…”

Section: Clinical Evidence For Hyperuricemia In Renal Diseasementioning

confidence: 99%

The conundrum of hyperuricemia, metabolic syndrome, and renal disease

et al. 2008

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The level of serum uric acid in human has been increasing over the last decades, and correlates with an increase prevalence of renal disease and metabolic syndrome. Understanding the role of uric acid in these conditions may provide clues for preventing the current epidemic of renal disease. Controversy still remains if hyperuricemia is simply a consequence or a cause of renal disease although epidemiological studies have attempted to resolve this issue. In this review, we discuss the clinical and experimental evidence for a causal role of hyperuricemia in renal diseases and potential relationships of hyperuricemia with metabolic syndrome.

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“…3 Sesso et al and Fernandes et al showed that most patients who start on RRT in our country is referred to nephrology services very late, and most are on stage 4 (47.3%), which contrasts with data in international literature, in which most patients are on stage 3. [3][4][5][6][7][8][9][10][11][12][13][14][15] Besides the expected contribution of age and CKD staging, the correlation of proteinuria with the progression of the renal disease, even if eased by the renoprotection by ACEI and ARB, is demonstrated in many studies. [16][17][18] This phenomenon is clearly observed in patients with type II DM, in which ¼ of the patients presents with renal compromise after ten years of disease.…”

Section: Discussionmentioning

confidence: 99%

“…6 It has recently been demonstrated that the correction of vitamin D deficiency, hyperuricemia and metabolic acidosis also lead to the decrease of GFR in patients with predialytic CKD. [7][8][9][10] This study aimed to assess the impact of demographic, clinical and laboratory variables that were present at admission and let to the outcomes death or renal replacement therapy (RRT) in patients with stages 3-5 CKD on conservative treatment.…”

Section: Introductionmentioning

confidence: 99%

Associação entre fatores de risco clínicos e laboratoriais e progressão da doença renal crônica pré-dialítica

Pereira¹,

Carminatti²,

Fernandes³

et al. 2012

J. Bras. Nefrol.

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ResumoIntrodução: A doença renal crônica (DRC) é muito prevalente e representa um importante problema de saúde pública. O maior conhecimento dos fatores de risco relacionados à progressão da DRC permite adotar estratégias terapêuticas que podem alterar o curso natural da doença. Objetivo: Avaliar o impacto de variáveis clínicas e laboratoriais à admissão nos desfechos de óbito e início de terapia renal substitutiva (TRS). Métodos: Estudo de coorte retrospectiva, composta de 211 pacientes adultos com DRC nos estágios 3-5 tratados, acompanhados por 56,6 ± 34,5 meses. Resultados: A idade média dos pacientes foi de 65,4 ± 15,1 anos, sendo 63,5% com > 60 anos. As principais etiologias de DRC foram nefroesclerose hipertensiva (29%) e doença renal diabética (DRD) (17%). A maioria dos pacientes encontravase no estágio 4 da DRC (47,3%). A perda média anual de taxa de filtração glomerular (TFG) foi 0,6 ± 2,5 mL/min/1,73 m 2 (mediana 0,7 mL/min/1,73 m 2 ). Após os ajustes para as variáveis demográficas, clínicas e laboratoriais, concluiu-se que apresentar DRD [risco relativo (RR) 4,4; intervalo de confiança (IC) 95%, 1,47-13,2; p = 0,008] foi preditor de TRS e a idade (RR 1,09; IC 95%, 1,04-1,15; p < 0,0001) e o não tratamento com bloqueador do receptor da angiotensina (BRA) (RR 4,18; IC 95%, 1,34-12,9; p = 0,01) foram preditores de ób-ito. A sobrevida renal e a geral dos pacientes foram de 70,9% e 68,6%, respectivamente. Conclusão: Neste estudo, os pacientes com DRC nos estágios 3-5 tratados conservadoramente apresentaram estabilização funcional e baixa mortalidade, desfechos associados à DRD, idade e não tratamento com BRA. Palavras-chave: Insuficiência renal crônica. Progressão da doença. Fatores de risco. AbstRActIntroduction: Chronic kidney disease (CKD) is a very common condition that has become a public health issue. Knowing more about risk factors associated with the progression of CKD allows therapeutic interventions that may change the natural course of the disease. Objective: To evaluate the impact of clinical and laboratory variables at admission on the outcomes death and need for renal replacement therapy (RRT). Methods: A retrospective cohort study comprised of 211 adult patients with stages 3-5 CKD, followed-up for 56.6 ± 34.5 months. Results: Mean age of patients was 65.4 ± 15.1 years and 63.5% were > 60 years. The main causes of CKD were hypertensive nephrosclerosis (29%) and diabetic kidney disease (DKD) (17%). Most patients (47.3%) were on stage 4 CKD. The mean annual loss of glomerular filtration rate (GFR) was 0.6 ± 2.5 mL/min/1.73 m 2 (median 0.77 mL/min/1.73 m 2 ) After the adjustments for demographic, clinical and laboratory variables, DKD [relative risk (RR) 4.4; 95% confidence interval (CI), 1.47 to 13.2; p = 0.008] was predictive of RRT; age (RR 1.09; 95% CI, 1.04 to 1.15; p < 0.0001) and the non-treatment with angiotensin receptor blocker (ARB) (RR 4.18, 95% CI, 1.34 to 12.9; p = 0.01) were predictors of death. Renal and patient survival rates were 70.9% and 68.6%, respectively. Conclusion: In t...

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Use of Allopurinol in Slowing the Progression of Renal Disease Through Its Ability to Lower Serum Uric Acid Level

Cited by 719 publications

References 26 publications

Uric Acid and the Development of Hypertension

Uric Acid and the Development of Hypertension

The conundrum of hyperuricemia, metabolic syndrome, and renal disease

Associação entre fatores de risco clínicos e laboratoriais e progressão da doença renal crônica pré-dialítica

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