Original Investigation
Pathogenesis and Treatment of Kidney Disease and Hypertension
Use of Allopurinol in Slowing the Progression of Renal Disease Through Its Ability to Lower Serum Uric Acid Level

https://doi.org/10.1053/j.ajkd.2005.10.006Get rights and content

Background: Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients. Methods: We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death. Results: One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 ± 1.18 mg/dL (0.58 ± 0.07 mmol/L) to 5.88 ± 1.01 mg/dL (0.35 ± 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015). Conclusion: Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

Section snippets

Methods

Eight hundred fifty-two patients were followed up in our renal clinic from April 2003 to April 2004 and screened for eligibility to participate in the study. Included subjects had to fulfill the following inclusion criteria: (1) presence of renal disease, defined as daily proteinuria greater than 0.5 g and/or an elevated serum creatinine (Cr) level greater than 1.35 mg/dL (>120 μmol/L) at baseline; and (2) in stable clinical condition in terms of general health and renal function (baseline

Results

Between April 2003 and April 2004, a total of 54 patients were enrolled in the study. Mean age of the allopurinol group was 47.7 ± 12.9 years, and of the control group, 48.8 ± 16.8 years. Male-female ratios were 9:4 and 13:15 for the treatment and control groups, respectively. Diabetes mellitus constituted 24% (treatment group) and 27% (control group) in our study population, and the majority of patients had preexisting hypertension (84%, treatment group; 73%, control group). Baseline

Discussion

Uric acid is a product of purine metabolism. After being filtered, uric acid is both reabsorbed and excreted in the proximal tubule through a voltage-sensitive urate channel and a urate-anion exchange mechanism. Hyperuricemia can be a result of either increased production or decreased excretion. In patients with renal disease, there is decreased uric acid urinary excretion, and whether this will give rise to hyperuricemia depends on the gastrointestinal excretory compensation.13 The prevalence

References (29)

  • S. Bo et al.

    Hypouricemia and hyperuricemia in type 2 diabetesTwo different phenotypes

    Eur J Clin Invest

    (2001)
  • L.H. Beck

    Requiem for gouty nephropathy

    Kidney Int

    (1986)
  • K. Iseki et al.

    Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects

    Hypertens Res

    (2001)
  • T. Nakagawa et al.

    Hyperuricemia causes glomerular hypertrophy in the rat

    Am J Nephrol

    (2003)
  • Cited by (0)

    Support: None. Potential conflicts of interest: None.

    Originally published online as doi:10.1053/j.ajkd.2005.10.006 on December 5, 2005.

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