Elsevier

Transplantation Proceedings

Volume 45, Issue 1, January–February 2013, Pages 387-390
Transplantation Proceedings

Thoracic transplantation
Complications
Iron Metabolism, Hepcidin, and Anemia in Orthotopic Heart Transplantation Recipients Treated with Mammalian Target of Rapamycin

https://doi.org/10.1016/j.transproceed.2012.02.040Get rights and content

Abstract

Purpose

Functional iron deficiency is characterized by the presence of adequate stores as defined by conventional criteria, but with the inability to sufficiently mobilize iron for erythropoiesis. Hepcidin, produced by hepatocytes in response to anemia, hypoxia, or inflammation, is a key regulator of iron homeostasis. Anemia is relatively common among patients treated with mammalian target of rapamycin (mTOR) antagonists. We tested hypothesis that hepcidin was related to the functional iron deficiency, defined as a ferritin value above 200 ng/mL with transform saturation (TSAT) below 20% among orthotopic heart transplant recipients (OHT) treated (n = 35) versus not treated (n = 134) with mTOR.

Methods and materials

Using standard laboratory methods we assessed iron status: serum iron, total iron binding capacity, ferritin, TSAT, complete blood count and creatinine. Soluble transferrin receptor (sTFR), high sensitivity C-reactive protein (hSCRP), interleukin-6 (IL-6) hepcidin, and cystatin C were measured using commercially available kits.

Results

According to the World Health Organization definition, the prevalence of anemia was 51% among mTOR treated whereas in the rest of the OHT the prevalence of anemia 30% among the other OHT patients. Functional iron deficiency was present in 80% of mTOR-treated patients. Serum hepcidin, IL-6, hsCRP, serum creatinine, cystatin C, NT-proBNP were significantly higher among mTOR treated patients; whereas sTFR, estimated glomerular filtration rate, hemoglobin, and erythrocyte count were significantly lower.

Conclusions

Functional iron deficiency which is common among OHT patients treated with mTOR, was associated with high hepcidin levels and inflammatory markers. This form of anemia in mTOR-treated OHT resembles the disorder of chronic disease, suggesting that OHT patients show low-grade inflammation, which should be investigated for underlying, potentially reversible causes. Iron treatment should also be considered.

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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