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      Four-Week Effects of Allopurinol and Febuxostat Treatments on Blood Pressure and Serum Creatinine Level in Gouty Men

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          Abstract

          The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.

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          Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.

          Yui-Pong Siu, Kay-Tai Leung, Matthew Tong … (2006)
          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. 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. 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). 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.
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            Preliminary criteria for the classification of the acute arthritis of primary gout.

            S L Wallace, H. Robinson, A T Masi … (1977)
            The American Rheumatism Association sub-committe on classification criteria for gout analyzed data from more than 700 patients with gout, pseudogout, rheumatoid arthritis, or septic arthritis. Criteria for classifying a patient as having gout were a) the presence of characteristic urate crystals in the joint fluid, and/or b) a topus proved to contain urate crystals by chemical or polarized light microscopic means, and/or c) the presence of six of the twelve clinical, laboratory, and X-ray phenomena listed in Table 5.
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              Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort.

              Kunitoshi Iseki, Yoshiharu Ikemiya, Taku Inoue … (2004)
              Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Korean Med Sci
                Journal ID (iso-abbrev): J. Korean Med. Sci
                Journal ID (publisher-id): JKMS
                Title: Journal of Korean Medical Science
                Publisher: The Korean Academy of Medical Sciences
                ISSN (Print): 1011-8934
                ISSN (Electronic): 1598-6357
                Publication date (Print): August 2014
                Publication date (Electronic): 30 July 2014
                Volume: 29
                Issue: 8
                Pages: 1077-1081
                Affiliations
                [1 ]Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
                [2 ]Institute for Skeletal Aging, Hallym University, Chunchun, Korea.
                [3 ]Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
                Author notes
                Address for Correspondence: Hyun Ah Kim, MD. Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 170-22 Gwanpyeong-ro, Dongan-gu, Anyang 431-070, Korea. Tel: +82.31-380-1826, Fax: +82.31-381-8812, kimha@ 123456hallym.ac.kr
                Author information
                http://orcid.org/0000-0002-9318-7446
                http://orcid.org/0000-0001-6550-3440
                http://orcid.org/0000-0002-5384-3437
                Article
                DOI: 10.3346/jkms.2014.29.8.1077
                PMC ID: 4129198
                PubMed ID: 25120316
                SO-VID: b61f5153-87be-4e03-baef-bd45f77f83b2
                Copyright © © 2014 The Korean Academy of Medical Sciences.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 09 January 2014
                Date accepted : 20 May 2014
                Funding
                Funded by: Hallym University Medical Center
                Award ID: 01-2010-12
                Categories
                Subject: Original Article
                Subject: Immunology, Allergic Disorders & Rheumatology

                ScienceOpen disciplines: Medicine
                Keywords: gout,hyperuricemia,allopurinol,febuxostat,creatinine,blood pressure
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: gout, hyperuricemia, allopurinol, febuxostat, creatinine, blood pressure

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