Sevelamer Decreases Serum Uric Acid Concentration through Adsorption of Uric Acid in Maintenance Hemodialysis Patients

Ohno, Iwao; Yamaguchi, Yoshihiro; Saikawa, Hajime; Uetake, Daijiro; Hikita, Miho; Okabe, Hideaki; Ichida, Kimiyoshi; Hosoya, Tatsuo

doi:10.2169/internalmedicine.48.1817

Cited by 31 publications

(20 citation statements)

References 18 publications

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“…It has been reported that sevelamer, a non-absorbable hydrogel, adsorbs uric acid nonselectively in the gastrointestinal tract, and decreases SUA in humans [46], [47]. This is consistent with the idea that the SUA level can be controlled by enhancing secretion of uric acid into intestinal lumen.…”

Section: Discussionsupporting

confidence: 86%

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

et al. 2012

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Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats.

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Section: Discussionsupporting

confidence: 86%

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

et al. 2012

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“…Sevelamer may be the phosphate binder of choice for patients with advanced CKD and gout, based on its urate-lowering effect 36,37 …”

Section: Tablementioning

confidence: 99%

Management of Gout and Hyperuricemia in CKD

Vargas-Santos

Neogi

2017

American Journal of Kidney Diseases

145

104

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Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal deposition, are common in patients with chronic kidney disease (CKD). While the presence of CKD poses additional challenges in gout management, effective urate-lowering is possible for most patients with CKD. Initial doses of urate-lowering therapy are lower than in the non-CKD population, while incremental dose escalation is guided by regular monitoring of serum urate to reach the target of less than 6 mg/dL (or less than 5 mg/dL for patients with tophi). Management of gout flares with presently available agents can be more challenging due to potential nephrotoxicity and/or contraindications in the setting of other common comorbidities. At present, asymptomatic hyperuricemia is not an indication for urate-lowering therapy, though emerging data may support a potential renoprotective effect.

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“…2,3 Decreased UA filtration due to reduced GFR, impaired UA tubular secretion caused by tubulointerstitial disease, and use of diuretics and cyclosporine (CsA) contribute to increased prevalence of HUA in CKD patients. 4 In terms of ethnic and gender differences, Asian patients with end-stage renal disease (ESRD) present higher rates of HUA 5 , and men have a higher risk of HUA and gout in the general population. 6 Data from several studies have associated HUA with increased incidence and/or progression of CKD.…”

Section: Introductionmentioning

confidence: 99%

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

et al. 2014

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The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

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Sevelamer Decreases Serum Uric Acid Concentration through Adsorption of Uric Acid in Maintenance Hemodialysis Patients

Cited by 31 publications

References 18 publications

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

Management of Gout and Hyperuricemia in CKD

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

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