Research paperHepcidin in anaemic geriatric patients with non-dialysis chronic kidney disease (ND-CKD)
Introduction
Anemia is highly prevalent in the elderly [1] and particularly in chronic kidney disease (CKD) with a stage dependent prevalence rate of more than 40% to > 70% [2], [3], [4]. Although data respecting prevalence of anemia in elderly non-dialysis chronic kidney disease (ND-CKD), patients are still rare, prevalence is supposed to be high, as CKD and anemia increase with age [1], [5]. Anemia is an acknowledged risk factor in pre-dialysis ND-CKD patients for morbidity with increased risk of cerebrovascular [6] and cardiovascular [7], [8], [9] events as well as the progression of CKD [10], [11].
Although pathogenesis of anemia in CKD is multifactorial involving inadequate erythropoietin production and iron-restricted erythropoiesis [12], a large number of CKD patients suffer from insufficient iron stores: analysis of CKD patients in the setting of the Third National Health and Nutrition Examination Survey (NHANES III) revealed that more than 40% of the patients with a glomerular filtration rate (GFR) < 60 mL/min did not have sufficient iron stores [13] to support erythropoiesis as judged by the National Kidney Foundation guidelines [14].
Hepcidin is a key regulator of iron homeostasis [15]: high concentrations of hepcidin inhibit intestinal iron absorption and iron release from macrophages and hepatocytes [16]. As the protein is renally released, it is likely to play a role in renal anemia, possibly causing a state of functional iron deficiency (i.e. iron deficiency with full iron stores) due to elevated serum hepcidin levels and consequently, an iron-restricted erythropoiesis. Treatment of iron deficiency in ND-CKD would avoid cost-intensive application of erythropoiesis stimulating agents (ESA) or reduce their dosage [17]. Although recent data shows that intravenous iron substitution is likely to be more effective than oral iron substitution in anaemic ND-CKD patients [18], it is no standard practice yet in these patients [19]. Considering the hepcidin mechanism, oral substitution remains challenging for this patient group due to limited enteral absorption and gastrointestinal side effects. Intravenous iron substitution offers an alternative, although side effects, like anaphylactic reactions can be associated. The improvement of therapeutic strategies in geriatric ND-CKD patients demands better understanding of the role of hepcidin in pathophysiology of ND-CKD. Recently, dependence of hepcidin serum levels on GFR has been shown in anaemic younger ND-CKD patients [20]. Our explorative study was therefore intended to analyse serum hepcidin levels in connection with haematological parameters and GFR in anaemic ND-CKD patients > 60 years.
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Material and methods
The study is of an explorative nature. Between February and June 2011, a number of 221 geriatric in-patients at our university hospital were consecutively screened. Among these patients, only 53 met with inclusion criteria: 22 (41.5%) men and 31 (58.5%) women. This patient cohort consisted of 42 patients with ND-CKD and 11 controls without ND-CKD. Selection criteria for patients according to groups 1–3 and 5 (Table 1) were:
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non-dialysis CKD;
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presence of anemia;
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TSAT < 16% (group 5: TSAT normal);
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Descriptive analysis
Anemia was found in all patients (group 1–3 and 5), except in control persons. TSAT was low in all patients of group 1–3 and normal in patients of group 5 as well as in all control persons. A slight cobalamin deficiency (180 pg/mL to 1100 pg/mL) with 169 pg/mL was found in one patient of group 2, but as neither megaloblastic anemia nor pancytopenia were present, no association of anemia with cobalamin deficiency was assumed. The patient therefore remained in group 2. Ferritin was low (< 30 μg/L) in
Discussion
Anemia is a frequent problem in elderly ND-CKD patients and association with functional iron deficiency is supposed. The role of hepcidin in connection with anemia in elderly ND-CKD patients is still unclear. A recent study of younger ND-CKD patients showed a dependence of serum hepcidin levels on GFR [20]: Zaritsky et al. managed to show an increase of serum hepcidin levels in association with a decrease of GFR in dependence of the KDOQI stage of ND-CKD patients < 40 years and they assumed a
Disclosure of interest
G. Röhrig and RJ. Schulz have received fees by Vifor Pharma for oral speech contributions at congress. V. Weiß and C. Nobbe state that there are no conflicts of interest.
Acknowledgements
The authors want to thank the German Geriatric Society (DGG) and the German Hemato-Oncologic Society (DGHO) for awarding this study the “Award of Scientific Advancement 2010” in Potsdam, Germany.
They further want to thank Dr. Alfred Janetzko for scientific support in Hepcidin ELISA analysis.
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