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      Effect of Fenofibrate in Combination with Urate Lowering Agents in Patients with Gout

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          Abstract

          Background

          To assess the efficacy of fenofibrate treatment in combination with urate lowering agents in patients with gout.

          Methods

          Fourteen male patients with chronic tophaceous or recurrent acute attacks of gout were evaluated in an open-label pilot study of the hypolipidemic agent, fenofibrate (Lipidil Supra® 160 mg/d). Patients were stable on urate lowering agents (allopurinol or benzbromarone) for ≥three months without acute attack for the most recent one month before participating. All patients were being treated with established doses of urate lowering agents without modification throughout the study. Clinical and biochemical assessments including serum uric acid, creatinine, liver function test and fasting serum lipid were measured at (1) baseline (2) after two months of fenofibrate treatment and (3) two months after fenofibrate was withdrawn.

          Results

          Serum uric acid was lowered by 23% after two months of fenofibrate treatment (6.93±2.16 vs. 5.22±1.16 mg/dL; p=0.016). Triglyceride levels were also reduced after fenofibrate treatment ( p=0.001). However, this effect was reversed after the withdrawal ( p=0.002) of the drug. Alkaline phosphatase was reduced after fenofibrate treatment ( p=0.006), but increased 21% after the withdrawal of the drug ( p=0.002). By contrast, serum levels of high density lipoprotein and creatinine were increased 9% ( p=0.018) and 12% ( p=0.006), respectively; however, both levels were significantly decreased to the baseline levels upon withdrawal of fenofibrate.

          Conclusions

          Fenofibrate can effectively reduce uric acid levels in addition to its known hypolipidemic effect. Fenofibrate may be used as a potential urate lowering agent in patients with gout, especially in those with coexisting hyperlipidemia.

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          Most cited references22

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          Regulation of renal urate excretion: a critical review.

          Uric acid metabolism is reviewed as it relates mainly to kidney and electrolyte disorders, with emphasis on the difficulties in understanding urate transport because of its bidirectional transport and the species differences in which animal data may not have relevance to the human condition. A critical review of the effects of pyrazinamide and extracellular volume expansion on urate transport raises questions about the current popular teachings that pyrazinamide exclusively blocks tubule urate secretion and extracellular volume expansion has a major role in controlling urate excretion. There appears to be a renal salt-wasting syndrome with overlapping clinical features that make it indistinguishable from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), except possibly for extracellular volume depletion. Hypouricemia and the elevation in the fractional excretion of urate (%E/Furate) are extensively reviewed with a proposal to use the persistence of hypouricemia and elevated %E/Furate after the correction of hyponatremia to differentiate these patients from those with SIADH. An algorithm is proposed to differentiate one group from the other. A plasma natriuretic factor has been shown in some with probable renal salt wasting, which includes patients with AIDS, cancer, and pulmonary and intracranial diseases. The natriuretic factor may have etiologic implications and diagnostic and therapeutic applications.
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            Epidemiology of gout: is the incidence rising?

            To determine whether the incidence of gout is higher in 1995-1996 compared to 1977-1978. Using the Rochester Epidemiology Project computerized medical record system, all potential cases of acute gout in the city of Rochester, Minnesota during the time intervals of 1977-1978 and 1995-1996 were identified. The complete medical records of all potential cases were screened and all who fulfilled the 1977 American College of Rheumatology proposed criteria for gout were included as incidence cases. Demographic data, body mass index, clinical presentation, and associated comorbid conditions were abstracted. The overall and age-gender adjusted incidence rates from the 2 cohorts were calculated and compared. A total of 39 new cases of acute gout were identified during the 2 year interval 1977-1978 representing an age and sex-adjusted annual incidence rate of 45.0/100,000 (95% CI: 30.7, 59.3). For the interval 1995-1996, 81 cases were diagnosed, representing an annual incidence rate of 62.3/100,000 (95% CI: 48.4, 76.2). There was a greater than 2-fold increase in the rate of primary gout (i.e., no history of diuretic exposure) in the recent compared to the older time periods (p = 0.002). The incidence of secondary, diuretic related gout did not increase over time (p = 0.140). Our results indicate that the incidence of primary gout has increased significantly over the past 20 years. While this increase might be a result of improved ascertainment of atypical gout, it may also be related to other, as yet unidentified, risk factors.
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              Fenofibrate for patients with asymptomatic primary biliary cirrhosis.

              Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology, the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation. However, only 20-30% of patients respond fully to UDCA. Recently, lipoprotein-lowering agents have been found to be effective for PBC. The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor alpha, in patients with aPBC. Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA. UDCA was used along with fenofibrate during the study. The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study. The serum levels of alkaline phosphatase (ALP) (285+/-114.8 IU/L) and immunoglobulin M (IgM) (255.8+/-85.9 mg/dl) significantly decreased to 186.9+/-76.2 IU/L and 192.9+/-67.5 mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover, the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients. Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone. Although the mechanism of fenofibrate on aPBC has not yet been fully clarified, combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its anti-inflammatory effect.
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                Author and article information

                Journal
                Korean J Intern Med
                Korean J. Intern. Med
                KJIM
                The Korean Journal of Internal Medicine
                The Korean Association of Internal Medicine
                1226-3303
                2005-6648
                June 2006
                30 June 2006
                : 21
                : 2
                : 89-93
                Affiliations
                Division of Rheumatology, College of Medicine, Ewha Womans University Seoul, Korea.
                [2 ]Division of Rheumatology, NHIC Ilsan Hospital, Kyonggi-do, Korea.
                Author notes
                Correspondence to: Jisoo Lee, M.D., Ph.D., Department of Internal Medicine, Ewha Womans University College of Medicine, 911-1 Mok-Dong, YangCheon-Gu, Seoul 158-710, Korea. Tel: 82-2-2650-6164, Fax: 82-2-2655-2076, leejisoo@ 123456ewha.ac.kr
                Article
                10.3904/kjim.2006.21.2.89
                3890742
                16913436
                1a3145eb-0284-4dfa-858d-65c699388123
                Copyright © 2006 The Korean Association of Internal Medicine

                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
                : 12 October 2005
                : 06 December 2005
                Categories
                Original Article

                Internal medicine
                fenofibrate,gout,hyperuricemia,hyperlipidemia
                Internal medicine
                fenofibrate, gout, hyperuricemia, hyperlipidemia

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