Effect of plasma uric acid on pharmacokinetics of cyclosporine A in living-related renal transplant recipients and pharmacokinetic study in rats with experimental hyperuricaemia

Sugioka, Nobuyuki; Takai, Mihoko; Yoshida, Kosuke; Yasuda, K; Fukushima, Keizo; Kokuhu, Takatoshi; Okamoto, Masahiko; Yoshimura, Norio; Takada, Kanji

doi:10.1111/j.1365-2710.2009.01105.x

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…It suggests that transplant recipients with high SUA may have poor absorption of CsA. [22] There are studies showing that CsA reduces glomerular filtration rate and leads to hyperuricemia. [2] Nonetheless, decreased secretion of uric acid in the proximal tubules might also contribute to high SUA.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors of hyperuricemia among kidney transplant recipients

Einollahi

Nafar

et al. 2013

Indian J Nephrol

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Hyperuricemia is common in renal transplant patients (RTRs), especially those on cyclosporine (CsA)-based therapy. We conducted a retrospective study to determine the prevalence of hyperuricemia and its risk factors among RTRs. A total of 17,686 blood samples were obtained from 4,217 RTRs between April 2008 and January 2011. Hyperuricemia was defined as an uric acid level of ≥7.0 mg/dl in men and of ≥6 mg/dl in women that persisted for at least two consecutive tests. Majority (68.2%) of RTRs were normouricemic. Hyperuricemia was more frequent in younger and female RTRs. On multivariate logistic regression, we found high trough level of cyclosporine to be a risk factor for hyperuricemia. In addition, female gender, impaired renal function, and dyslipidemia (hypercholesterolemia, hypertriglyceridemia, and elevated LDL) were also associated with higher probability of hyperuricemia. Hyperuricemia is a common complication after renal transplantation. Risk factors implicated in post-transplant hyperuricemia include high trough level of cyclosporine, female gender, renal allograft dysfunction, and dyslipidemia.

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Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors of hyperuricemia among kidney transplant recipients

Einollahi

Nafar

et al. 2013

Indian J Nephrol

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“…The occurrence of HUA is currently thought to be caused by a decrease in UA excretion, which can be accounted for increased reabsorption and/or decreased secretion of UA by the proximal tubules, but its molecular mechanism is still unclear (Ben Salem, Slim, Fathallah, & Hmouda, 2017; Gibson, 2013; Sugioka et al, 2010). UA is the end product of purine metabolism, the plasma concentration of which can be affected by the disturbances in purine metabolism, abnormal energy metabolism, and renal excretion disorders of UA.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of Arhalofenate in alleviating hyperuricemia―Activating PPARγ thereby reducing caspase‐1 activity

Wang

Zuo

2020

Drug Development Research

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Hyperuricemia (HUA) is an important risk factor for renal diseases and contributes to gout. Arhalofenate (Arha) has been proved to have uricosuric activity as an inhibitor of URAT1, organic anion transporter 4 (OAT4) and OAT10. However, the effects of Arha on HUA remain unknown. The objective of this study was to investigate whether Arha could alleviate HUA and uncovered the underlying mechanism in vitro. HK‐2 cells were exposed to uric acid (UA) to simulate HUA in vitro. Then cells were treated with Arha, caspase‐1 inhibitor Belnacasan (Beln), caspase‐11 inhibitor Wedelolactone (Wede) and PPARγ inhibitor Mifobate, respectively. The alteration of cell proliferation, inflammation, pyroptosis and expression of related proteins were detected. Results showed that UA exposure inhibited cell viability and increased IL‐1β and IL‐18 generation in a concentration dependent manner. Meanwhile, UA activated the cleavage of gasdermin D (GSDMD), enhanced the protein expression of URAT1, OAT4, TLR4, caspase‐1, and caspase‐11 and reduced PPARγ expression. While the presence of Arha or Beln enhanced cell viability and inhibited cleavage of GSDMD. Wede slightly increased cell viability but failed to prevent GSDMD cleavage. The expression of related proteins except caspase‐11was also recovered by Arha. Beln and Wede partially rescued related proteins level except PPARγ compared with model group. Besides, the co‐treatment of Mifobate blunted the effects of Arha on cell viability and expression of GSDMD, TLR4, and caspase‐1. In conclusion, Arha inhibited UA transport as well as preventing inflammation and pyroptosis via activating PPARγ thereby blocking caspase‐1 activation of HUA in vitro.

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Gout and Organ Transplantation

Stamp

Chapman

2012

Curr Rheumatol Rep

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Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use.

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Effect of plasma uric acid on pharmacokinetics of cyclosporine A in living-related renal transplant recipients and pharmacokinetic study in rats with experimental hyperuricaemia

Cited by 6 publications

References 28 publications

Prevalence and risk factors of hyperuricemia among kidney transplant recipients

Prevalence and risk factors of hyperuricemia among kidney transplant recipients

The mechanism of Arhalofenate in alleviating hyperuricemia―Activating PPARγ thereby reducing caspase‐1 activity

Gout and Organ Transplantation

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