Immunosuppressive Agents and Metabolic Factors of Cardiovascular Risk in Renal Transplant Recipients

Sessa, A.; Esposito, A.; Giliberti, A.; Iavicoli, G.; Costa, Cristina; Bergallo, Massimiliano; Lettieri, E.; Rossano, R.; Capuano, M.

doi:10.1016/j.transproceed.2009.02.045

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…Several studies investigating the potential mechanisms underlying the pathogenesis of new-onset diabetes following tacrolimus-based treatments had focused on insulin-resistance [ 8 , 10 , 33 – 37 ]. Alterations in peripheral insulin-signaling have been also reported in response to other immunomodulators, including rapamycin, cyclosporine A, and steroids [ 38 – 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tacrolimus (also known as fujimycin and FK506) is a macrolide lactone isolated from Streptomyces tsukubaensis , currently used as potent immunosuppressant in organ transplantation to reduce rejection rates [ 1 , 2 ]. One of its most common adverse effects is new-onset diabetes mellitus following transplantation [ 3 – 7 ], a serious complication that also increases the risk of infection and cardiovascular disease [ 8 ]. Indeed, a 5-year follow-up study monitoring patients treated with tacrolimus after transplant revealed an incidence of diabetes of 41% [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

et al. 2017

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BackgroundOne of the most common side effects of the immunosuppressive drug tacrolimus (FK506) is the increased risk of new-onset diabetes mellitus. However, the molecular mechanisms underlying this association have not been fully clarified.MethodsWe studied the effects of the therapeutic dose of tacrolimus on mitochondrial fitness in beta-cells.ResultsWe demonstrate that tacrolimus impairs glucose-stimulated insulin secretion (GSIS) in beta-cells through a previously unidentified mechanism. Indeed, tacrolimus causes a decrease in mitochondrial Ca2+ uptake, accompanied by altered mitochondrial respiration and reduced ATP production, eventually leading to impaired GSIS.ConclusionOur observations individuate a new fundamental mechanism responsible for the augmented incidence of diabetes following tacrolimus treatment. Indeed, this drug alters Ca2+ fluxes in mitochondria, thereby compromising metabolism-secretion coupling in beta-cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

et al. 2017

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“…mTOR inhibitors have been associated with a lower risk of hypertension compared to calcineurin inhibitors when used in solid organ transplant recipients ( 137 , 156 ). The difference between effects of CNI and mTOR inhibitors is likely driven by multiple mechanisms with an overall vasodilatory effect of mTOR inhibitors ( 157 , 158 ). Sirolimus and everolimus appear to increase nitric oxide production preventing endothelial hyperplasia and dysfunction ( 133 , 134 ).…”

Section: Hypertensionmentioning

confidence: 99%

Cardiovascular effects of immunosuppression agents

Elezaby

Dexheimer

Sallam

2022

Front. Cardiovasc. Med.

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Immunosuppressive medications are widely used to treat patients with neoplasms, autoimmune conditions and solid organ transplants. Key drug classes, namely calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and purine synthesis inhibitors, have direct effects on the structure and function of the heart and vascular system. In the heart, immunosuppressive agents modulate cardiac hypertrophy, mitochondrial function, and arrhythmia risk, while in vasculature, they influence vessel remodeling, circulating lipids, and blood pressure. The aim of this review is to present the preclinical and clinical literature examining the cardiovascular effects of immunosuppressive agents, with a specific focus on cyclosporine, tacrolimus, sirolimus, everolimus, mycophenolate, and azathioprine.

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“…Одним из наиболее значимых осложнений у пациентов с пересадкой почки являются дислипопротеинемии (ДЛП), приводящие к поражению сердечно-сосудистой системы, на долю которых приходится 35-50% летальных исходов [1]. Известно, что ДЛП являются следствием применения циклоспорина А или такролимуса.…”

Section: Introductionunclassified

Diagnosis of Type IV Dyslipoproteinemia in Patients with Hypertriglyceridemia after Kidney Transplant Received Tacrolimous

Щастный,

Осочук,

Марцинкевич

et al. 2024

Хирургия. Восточная Европа

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Цель. Разработать расчетный метод отнесения пациентов, применяющих такролимус после пересадки почки, к категории лиц с повышенным содержанием ХС ЛПОНП как альтернативу использующемуся в клинической практике методу В.Т. Фридвальда. Материалы и методы. В группу обследуемых пациентов включены 15 мужчин (36–60 лет) и 15 женщин (36–55 лет) второго периода зрелого возраста. В контрольную группу вошли по 15 здоровых мужчин и женщин того же возраста. Всего проанализировано 55 человек – 30 здоровых лиц обоего пола и 25 (без выпадения исследуемых показателей) – с пересадкой почки на 7-е сутки после операции. ЛПОНП выделяли методом препаративного ультрацентрифугирования. Количество ХС и ТГ ЛПОНП, глюкозы, креатинина, мочевины плазмы крови, активности АсАТ и АлАТ определяли с использованием биохимических наборов. Статистический анализ выполнен с применением пакета прикладных программ R 4.2.2. Результаты. Разработана модель отнесения пациентов, применяющих такролимус после пересадки почки, к категории лиц с повышенным содержанием ХС ЛПОНП. Заключение. Разработанная нами логистическая модель позволяет отнести пациентов в возрасте 36–60 лет для мужчин и 36–55 лет для женщин на 7-е сутки после пересадки почки к лицам с повышенным или сниженным уровнем ХС ЛПОНП вне зависимости от содержания ТГ в крови без использования расчетного метода, предложенного В.Т. Фридвальдом. Purpose. To develop a calculation method for classifying patients using tacrolimus after kidney transplantation as those with elevated VLDL-C. As an alternative to the V.T. Fridwald method used in clinical practice. Materials and methods. The group of examined patients included 15 men (36–60 years old) and 15 women (36–55 years old) of the second period of adulthood. The control group included 15 healthy men and women of the same age. A total of 55 people were analyzed – 30 healthy people of both sexes and 25 patients (without loss of the studied parameters) with a kidney transplant on the 7th day after the operation. VLDL was isolated by preparative ultracentrifugation. The amount of cholesterol and TG of VLDL, glucose, creatinine, blood plasma urea, activity of AST and ALT was determined using biochemical kits. Statistical analysis was performed using the application package R 4.2.2. Results. A model was developed to classify patients using tacrolimus after kidney transplantation as individuals with elevated VLDL cholesterol levels. Conclusion. The logistic model developed by us makes it possible to classify patients aged 36–60 years for men and 36–55 years for women on the 7th day after kidney transplantation as persons with elevated or reduced levels of VLDL-C, regardless of the content of blood triglycerides without using the calculation method proposed V.T. Friedwald.

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Immunosuppressive Agents and Metabolic Factors of Cardiovascular Risk in Renal Transplant Recipients

Cited by 12 publications

References 37 publications

Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

Cardiovascular effects of immunosuppression agents

Diagnosis of Type IV Dyslipoproteinemia in Patients with Hypertriglyceridemia after Kidney Transplant Received Tacrolimous

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