Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation / Deficiência funcional de ferro em pacientes em hemodiálise: prevalência, avaliação nutricional e de biomarcadores de estresse oxidativo e de inflamação

Abstract Introduction: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. Objectives: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. Statistical analysis: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. Results: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). Discussion: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Resumo Introdução: A anemia na DRC pode ser dividida em anemia sem deficiência funcional de ferro e com deficiência funcional de ferro (ADFF). Diante do aumento dos casos de hemossiderose em pacientes em hemodiálise, atribuídos à reposição excessiva de ferro endovenoso, maiores conhecimentos sobre os fatores envolvidos na gênese da ADFF são importantes. Objetivos: documentar a prevalência de ADFF em renais crônicos em hemodiálise. Caracterizar clínica e laboratorialmente os portadores de ADFF em HD e avaliar o estado nutricional, estresse oxidativo e inflamatório. Estudo transversal, amostra de conveniência, envolvendo 183 renais crônicos em hemodiálise no sul do Brasil. Após aplicação dos critérios de exclusão, os pacientes foram separados em dois grupos: portadores de anemia com e sem deficiência funcional de ferro. Foram submetidos a questionário socioepidemiológico, à análise antropométrica e análise laboratorial dos marcadores de anemia, estresse oxidativo, inflamatórios e nutricionais. Análise estatística: programa GraphPad InStat versão 3.1. Foram aplicados os testes: Kolmogorov-Smirnov, qui-quadrado, t de Student e Mann-Whitney. Nível de significância adotado de 5%. Resultados: não houve diferença significativa nos marcadores inflamatórios entre os dois grupos. Houve diferença significativa nos marcadores de anemia e nutrição, significativamente menores nos pacientes com ADFF. Pacientes com ADFF receberam doses mais elevadas de ferro parenteral (p < 0,05). Discussão: ADFF esteve associada a menores valores de marcadores nutricionais, mas não esteve associada a marcadores inflamatórios ou de estresse oxidativo aumentados, como relatado na literatura. Estudos adicionais sobre o tema são necessários.

Deferasirox: Oral, once daily iron chelator - An expert opinion.

Iron overload is a serious and potentially fatal condition that results from multiple blood transfusions required over a long period of time to treat certain types of anemias such as, that caused by β-thalassemia, sickle cell disease and myelodysplastic syndrome. Deferoxamine, which has been used since four decades as an iron chelator has limited efficacy due to its demanding therapeutic regimen, leading to poor compliance. Deferasirox, once daily oral iron chelator provides an effective alternative to Deferoxamine in the treatment of transfusional hemosiderosis. In this review, the role of Deferasirox as an ideal iron chelator has been discussed. Pubmed searches on Deferasirox were carried out for the same. Several studies demonstrated the safety and efficacy of Deferasirox in reducing iron burden in iron-overloaded patients with β-thalassemia, sickle cell anemia and myelodysplastic anemia. Thus, convenient, effective and tolerable chelation therapy with oral Deferasirox is likely to be a significant development in the treatment of transfusional iron overload, due to its ability to provide constant chelation coverage and the potential to improve compliance.

Liver tissue injury secondary to iron overload in beta-thalassemia/hemoglobin E disease.

Liver tissues from 17 patients with advanced stages of beta-thal/Hb E disease were examined by light and electron microscopy, with emphasis on cellular damage due to excess iron overload. Various histochemical stains were performed to grade degrees of iron deposition and fibrosis, and to demonstrate hepatitis B surface antigen, in Kupffer cells as well as macrophages. The results of light and electron microscopic studies were correlated. There was a variation in the distribution of hepatic iron and the severity of fibrosis. In most of the cases ballooning degeneration of the hepatocytes, increase in number of lysosomes, hemosiderin and ferritin in hepatocytes as well as in the sinusoidal lining cells were found. The ferro-acidophilic body, representing another important form of hepatocellular necrosis also occurred. So far no precise mechanisms can be concluded.