Thoracic transplantationComplicationsIron Metabolism, Hepcidin, and Anemia in Orthotopic Heart Transplantation Recipients Treated with Mammalian Target of Rapamycin
Section snippets
Patients and Methods
The study included 169 patients including 35 females who underwent their first OHT. The patients' characteristics are shown in Table 1. Only 18 displayed diabetes mellitus. Indications for OHT were: ischemic cardiomyopathy (n = 98), dilated cardiomyopathy (n = 64), or end-stage valvular disease (n = 7). All the patients were transplanted according to the Shumway-Cooley-Brock technique. Prior to OHT serum creatinine in all the patients was below 162 μmol/L (1.8 mg/dL). In 20% of them induction
Results
The clinical and biochemical parameters of OHT patients with regard to mTOR treatment are shown in Table 1. Serum hepcidin, IL-6, hsCRP, serum creatinine, cystatin C, NT-proBNP were significantly higher whereas sTFR, estimated GFR (any formula) and Hb, were significantly lower among patients treated with an mTOR antagonist. According to the WHO definition, the prevalence of anemia was 51% among OHT patients treated with mTOR; the others displayed a 30% prevalence. Functional iron deficiency
Discussion
In our previous study the 41% prevalence of anemia was relatively high.5 Multiple regression analysis revealed the only predictor for anemia to be kidney function in this population, resembling the situation in renal allograft recipients, where the most frequent underlying cause is allograft dysfunction. Taegtmeyer et al6 reported that anemia before, but not after transplantation, was an independent predictor of 1-year survival.
Data on iron status in heart allograft recipients are limited.
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Cited by (21)
Hyperactivation of mTOR and AKT in a cardiac hypertrophy animal model of Friedreich ataxia
2022, HeliyonCitation Excerpt :Furthermore, the pleiotropic effects of rapamycin are of significant concern. Clinical studies have shown that chronic treatment with rapamycin are associated with the development of microcytic anemia (Przybylowski et al., 2013). We observed a marked decrease in TfR1 levels in Fxn cKO mice after 3–6 weeks of diet containing 42 ppm rapamycin, although no changes in other iron metabolism factors including Irp1, Irp2 and Fpn1 were observed (Figure 6B).
Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial
2021, Journal of Heart and Lung TransplantationCitation Excerpt :Knowledge regarding iron metabolism in heart transplant recipients is limited. Recipients treated with inhibitors of mammalian target of rapamycin exhibit higher levels of hepcidin and IL-6.24 In our population, we use prednisolone and a calcineurin inhibitor (cyclosporine) more often than mammalian target of rapamycin inhibitors.
The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes
2020, Archives of Biochemistry and BiophysicsCitation Excerpt :In addition to the action of ferrostatin-1, ferroptosis in cardiomyocytes could also be prevented by augmented mechanistic target of rapamycin (mTOR) signaling, overexpression of ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP2), and administration of puerarin (a bioactive compound extracted from a Chinese medicinal plant Pueraria lobata) (Table 5) [35,36,49]. It has been reported that mTOR regulates iron homeostasis by modulating transferrin receptor 1 (TfR1) stability [50,51]. As TfR1 is one of the major pathways of iron entry into the cell, it has been hypothesized that ferroptosis could be modified via alterations of mTOR activity.
Autophagy as a pharmacological target in hematopoiesis and hematological disorders
2018, Biochemical PharmacologyCitation Excerpt :Relapsed/refractory AML patients treated using a rapamycin (14) or rapalogs in combination with conventional chemotherapy (everolimus/azacitidine, sirolimus/MEC (mitoxantrone/etoposide/cytarabine), temsirolimus/clofarabine, etc.) showed a considerable increase in the overall remission rate [166–168]. In addition to their antileukemic and strong immunosuppressive effects, rapamycin (14) and rapalogs display many adverse events, such as dermatologic, metabolic, renal, pulmonary, blood, and wound healing disorders, anemia and hypertension [169–171]. Moreover, inhibition of mTOR also leads to feedback regulation, resulting in PI3K and ERK activation, which limits the anti-tumor effect of rapalogs (Fig. 3) and, eventually, resistance.
Disturbances in iron homeostasis result in accelerated rejection after experimental heart transplantation
2017, Journal of Heart and Lung TransplantationMammalian target of rapamycin coordinates iron metabolism with iron-sulfur cluster assembly enzyme and tristetraprolin
2014, NutritionCitation Excerpt :The essential role of mTOR in iron metabolism was established because clinical use of rapamycin is associated with the development of microcytosis and polyglobulia, which is mechanistically distinct from the anemia of chronic disease [28,29]. According to the World Health Organization definition, functional iron deficiency was present in 80% of mTOR-treated orthotopic heart transplant patients [30]. There are two mechanisms that can be used to analyze how the mTOR pathway serves to modulate iron metabolism and homeostasis: Through phosphorylation stabilizing ISCU protein and inhibiting TTP expression separately.