P1407liver, Heart and Bone: The Path of Iron Overload in Hemodialysis Patients

Abstract

Background Chronic kidney disease (CKD) is associated with several comorbidities, including anemia, since with decreased renal function there is a decrease in erythropoietin (EPO) production and changes in iron (Fe) metabolism. In hemodialysis patients, prescription of Fe is indicated to supplement the needs of this element by maintaining ferritin levels above 100 mg/dl and transferrin saturation greater than 20%. However, the excess of Fe can generate free Fe not bound to transferrin, and deposit in organs such as liver, heart, and bone marrow, with consequent impairment of their function. In hemodialysis patients, the diagnosis of Fe overload, its clinical significance and therapeutic decision have been poorly studied, unlike thalassemia patients. Aims To assess whether hemodialysis patients with ferritin levels equal to or greater than 1000 mg/l also have Fe overload in liver, heart, and bone marrow, as well as compromise bone density and remodeling. Method This is a cross-sectional analysis that included 28 adult patients on regular conventional hemodialysis. Inclusion criteria were serum levels of ferritin ≥ 1000 mg/l, and ESRD treated by regular hemodialysis for at least 6 months. We excluded patients with HIV, cancer, hepatic disease, patients who received desferroxamine in the latest year, and those previously submitted to a kidney transplant. All patients underwent dual-energy X-ray absorptiometry (DXA), serum ferritin, transferrin saturation index (STI), Fe, C reactive protein (CRP), Calcium(Ca), phosphorus (P), parathyroid hormone (PTH) and alkaline phosphatase (AP) levels were recorded. T2* image acquisition of Magnetic Resonance Imaging (MRI) 1,5 Tesla, were used for the assessment of Fe of liver, and heart. R2* and R2* Water were used of liver and bone (iliac crest). Bone biopsy was also performed. Results We evaluated 28 hemodialysis patients with a mean age of 55.8±13.1, hemodialysis time of 42.5±26.5 and iron use in the year prior to study enrollment of 311.5±179.8 mg/month. Biochemical analysis showed 3 patients with Hb below 9.0 mg/dl and 14 with values above 11.5 mg/dl; 6 patients with SatFe <30% and 12 patients with ferritin >1500mg/dl; 16 patients with PTH <300pg/ml and eight with >600pg/dl. MRI revealed Fe overload in the liver and bone tissue (figure 1) of all patients but not in the heart. Serum ferritin levels correlated with liver and bone overload (figure 2). Densitometry and bone biopsy results were not affected by Fe overload, however, serum Fe levels were associated with lower bone remodeling and mineralization suggesting an effect of this element on osteoblast activity. Conclusion High serum ferritin is associated with liver and bone marrow Fe overload, but not heart, as well as with low bone remodeling and mineralization. We must be aware of these side effects of high doses of Fe that are commonly used in these patients.