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Post-mortem liver and bone marrow iron quantification in haemodialysis patients: A prospective cohort study.

Patricia Carrilho,Pedro Fidalgo,Anna Lima, Lourdes Bastos, Elisa Soares,Rita Manso, Alexandra Santos,Lucinda Nobrega

EBioMedicine(2022)

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Abstract
BACKGROUND:Magnetic resonance liver scans indicate that iron overload is common in haemodialysis (HD) patients. However, histological evidence is scarce. METHODS:Liver biopsy and bone marrow aspirate were obtained in the first 24h post mortem from 21 adult HD patients. Biochemical liver iron content (LIC) was quantified by electrothermal atomization atomic absorption spectrophotometry. Tissue iron deposition was graded in the liver and bone marrow using Scheuer and Gale's criteria, respectively. FINDINGS:Median LIC was 42.5 (22.9-69.7) μmol/g and the majority (n=11; 57%) had mild to moderate liver iron overload (LIC >36 μmol/g). Scheuer grade was 2 (1-3) and 13 (62%) of liver biopsies had increased (> 1) iron deposition. In the bone marrow, median Gale's grade was 3 (3-4) and 9 (45%) patients had increased (>3) iron content. Contrary to old autopsy studies, done in the pre-erythropoiesis-stimulating agents (ESAs) era, both liver and bone marrow were iron replete and showed a positive correlation (r=0.71, p<0.001). Ferritin proved to have a good diagnostic accuracy for liver iron overload (0.87 95% CI 0.71-1.00) with an optimal cut-off value of 422 ng/ml. Haemoglobin was negatively associated with both LIC (r= -0.46, p=0.04) and iron content in the bone marrow (p=0.04). Patients with increased LIC had higher resistance to ESAs (p=0.02), yet no association with previous IV iron therapy. INTERPRETATION:In the majority of HD patients there was iron accumulation in both the liver and bone marrow that associated with anaemia severity and resistance to ESAs, suggesting a blocking mechanism of iron's utilization. FUNDING:None.
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