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Jimeno L, Rodado R, Campos M, Lanuza M.
Transplant Proc. 2005 Mar;37(2):1007-8.
The state of iron deposits in long-term kidney graft recipients is not well-known. Angiotensin enzyme inhibitors (ACEIs) reduce hematocrit levels in patients with posttransplant erythrocytosis (PTE), but their action on iron deposits has not been sufficiently evaluated. We designed this study to investigate the prevalence of iron deficiency among patients without anemia, the efficacy of ACEI treatment and its influence on iron deposits, and the risks of iron treatment in patients with symptomatic iron deficiency but no anemia. One hundred thirty eight patients were included if they had a kidney transplant for more than a year, with good renal function, with no anemia, and with neither iron nor rHuEpo, ARA, or ACEI treatment. One hundred seventeen had a normal Ht (group 1) and 21 had PTE (group 2). Iron deficiency was found in 73 (62.4%) group 1 patients and in 10 (47%) group 2 patients. Two group 1 patients with symptoms of iron deficiency were treated with oral iron. Their symptoms disappeared, but one developed PTE. Enalapril treatment decreased Ht levels in PTE but not in control patients. Furthermore, this drug increased iron deposits in PTE and controls with a baseline iron deficiency. We conclude that there is a high prevalence of iron deficiency in long-term transplanted patients without anemia. Furthermore, iron treatment must be carefully administered because of the risk of PTE. Enalapril treatment decreased Ht levels in PTE but not in control patients and increased iron deposits in patients with baseline iron deficiency.
ITO rating/ comment
In this non-randomized study in long-term kidney graft recipients, the prevalence of iron deficiency was shown to be present in 62.4% of patients with normal hematocrit levels, and 47% in patients with posttransplant erythrocytosis (PTE). Enalapril decreased serum ferritin and transferrin saturation in patients with PTE. Only two patients, both with normal hematocrit (Hct), received iron therapy; one developed PTE. Therefore, although the authors recommend careful monitoring of iron status and Hct during oral iron therapy in posttransplant patient with iron deficiency, the conclusions that could be drawn from this study with regard to iron therapy are rather limited. The authors recommend that further studies be undertaken in order to examine the incidence of iron deficiency in long-term kidney graft recipients with a normal Hct or with PTE.
Reviewed by: ITO
Overview
Background: Patients with chronic renal failure (CRF) often present with iron deficiency, this is especially the case for patients who have undergone kidney transplantation. Studies have examined the state of iron stores in kidney graft recipients with anemia, but not in long-term transplanted patients without anemia or posttransplant erythrocytosis (PTE). It is not known in what way angiotensin-converting enzyme inhibitors (ACEIs) modify iron stores, although it is known that they reduce hematocrit (Hct) levels in patients with PTE. There is also a lack of studies concerning the safety of iron supplementation in nonanemic iron deficient patients.
The objectives of the present study were triple: to evaluate the prevalence of iron deficiency among nonanemic transplant patients; evaluate the efficacy of ACEI treatment on erythrocytosis and on iron stores; the risks of iron supplementation in iron deficient nonanemic patients.
Methods: Patients who had had a graft kidney for over a year were included in the study if they corresponded to the following inclusion criteria: creatinine (Cr) serum level < 2 mg/dL, nonanemic, were not undergoing iron, erythropoietin, ACEI or ARA treatment. Two groups were formed according to hematocrit (Hct) levels: group 1 (n = 117) had normal hematocrit (Hct), group 2 (n = 21) had PTE, which was defined as Hct > 51%. Iron deficiency was defined as transferrin saturation (TSAT) < 20% and/or a serum ferritin (SF) level < 40 µg/L.
Hair loss, glossitis, cheilitis, or asthenia were used to evaluate the severity of iron deficiency. Iron deficient patients were administered 525 mg/day of ferrum sulphate until disappearance of symptoms. Twenty patients in group 1, and 21 patients in group 2 received 2.5-5 mg/d of enalapril. TSAT, SF, and Hct were recorded before and 15, 30, 90, 180, and 365 days after enalapril treatment.
Results: Iron deficiency was reported in 73 patients (62.4%) in group 1, and in 10 (47%) of patients in group 2. Enalapril treatment was found to significantly decrease Hct in PTE patients (p < 0.025) but not in patients with normal Hct (group 1, controls). Enalapril treatment – administered to 21 PTE patients and 20 patients with normal Hct – increased TSAT and SF in PTE patients, and increased TSAT in those in the control group who had iron deficiency (p < 0.05). In non-iron deficient patients in both groups, enalapril treatment did not affect TSAT and SF.
Two patients from group 1 presented with symptoms of iron deficiency: glossitis and asthenia in one, and hair loss in the other. These patients received 525 mg/day of ferrum sulphate until symptoms disappeared, ;however one patient developed PTE withPTE with Hct increasingfromincreasing from 42% to 59% 2 months after initiation of treatment.
Conclusion: The authors conclude that the prevalence of iron deficiency was far greater than had been expected in long-term kidney graft recipients. Enalapril increases iron stores in patients with baseline iron deficiency.
Key Points
· Almost 50% of transplanted patients present with iron deficiency in the early posttransplantation period.
· More studies are required to examine the incidence of this iron deficiency in long-term kidney graft recipients with a normal Hct or with PTE.
· In long-term kidney graft recipients, iron therapy might be beneficial, but strict control of SF and hematocrit levels is recommended to avoid the risk of PTE.
· Low doses of enalapril decreased the Hct levels only in PTE patients.
· Enalapril treatment increased iron stores in patients with iron deficiency probably because of its inhibitory action on erythropoiesis.
Limitations
· Non-randomized trial.
· Small group of patients, with particularly few who received enalapril (n = 41) and even less who received iron therapy (n = 2).
· The authors do not provide the full data of the study.
· Only a small number of patients were administered iron therapy.