Resistance of dialyzed patients to erythropoietin.

Resistance to recombinant human erythropoietin is a common condition in dialyzed patients with chronic kidney disease and is associated with more hospitalizations, increased mortality and frequent blood transfusions. The main cause of hyporesponsiveness to recombinant human erythropoietin in these patients is iron deficiency. However, a high proportion of patients does not respond to treatment, even to the use of intravenous iron, which indicates the presence of other important causes of resistance. In addition to the iron deficiency, the most common causes of resistance include inflammation, infection, malnutrition, inadequate dialysis, and hyperparathyroidism, although other factors may be associated. In the presence of adequate iron stores, other causes should be investigated and treated appropriately.

Resistance of dialyzed patients to erythropoietin

Resistance to recombinant human erythropoietin is a common condition in dialyzed patients with chronic kidney disease and is associated with more hospitalizations, increased mortality and frequent blood transfusions. The main cause of hyporesponsiveness to recombinant human erythropoietin in these patients is iron deficiency. However, a high proportion of patients does not respond to treatment, even to the use of intravenous iron, which indicates the presence of other important causes of resistance. In addition to the iron deficiency, the most common causes of resistance include inflammation, infection, malnutrition, inadequate dialysis, and hyperparathyroidism, although other factors may be associated. In the presence of adequate iron stores, other causes should be investigated and treated appropriately.

Parvovirus B19 (B19) and cytomegalovirus (CMV) infections and anti-erythropoietin (anti-EPO) antibodies in patients on dialysis hyporesponsive to erythropoietin therapy.

BACKGROUND: Approximately 10% of patients receiving recombinant human erythropoietin (rHuEPO) do not respond to the treatment. We evaluated parvovirus B19 (B19) and cytomegalovirus (CMV) infections and antierythropoietin (anti-EPO) antibodies as potential causes of anemia in dialyzed patients, hyporesponsive to rHuEPO. METHODS: Data from 120 dialyzed patients, receiving rHuEPO alfa, were collected: demographic characteristics, rHuEPO dose, duration of rHuEPO treatment and time on dialysis, etiology of chronic kidney disease and transfusion history. Serology and PCR were performed to address B19 and CMV infection status. An ELISA was developed to detect anti-EPO antibodies. RESULTS: rHuEPO resistance correlated with high ferritin levels (p = 0.001) and short time on dialysis (p = 0.012). B19 DNA was found in 10 (8.3%) dialyzed patients and CMV DNA was detected in 33 (27.5%). There was no significant correlation between B19 infection and anemia,while a tendency of correlation between active CMV infection and hemoglobin levels or hematocrit value (p= 0.069 and p= 0.070, respectively) has been observed. Anti-EPO antibodies were not detected in any patient. CONCLUSIONS: B19 infection is a rare complication in dialyzed patients and should be investigated after exclusion of other common causes, while CMV infection is rather common. The role of CMV infection in the hyporesponsiveness in dialyzed patients should be further evaluated in other studies. Our data suggest that anti-EPO antibodies are not involved in rHuEPO resistance in this population.

Cytokines signatures in short and long-term stable renal transplanted patients.

Despite the evidences showing the relevance of regulatory immune-mediated mechanisms to guarantee the stable graft function in renal transplanted patients, studies focusing on the immune response observed over a long-term period after renal transplantation are still limited. Several efforts have been done to establish novel biomarkers with relevant predictive values that could be used as prognostic laboratorial tools to monitor the complex network triggered through time after kidney transplantation. In this study, we have evaluated the pro-inflammatory and regulatory patterns of plasma cytokines in a group of 120 renal transplanted patients with stable graft function ranging from 1 to 160 months. Our data demonstrated an overall predominance of regulatory cytokines short-term after renal transplantation (1-24 months) with peaks of IL-4, IL-5 and IL-10. Moreover, a slight peak of TNF-α was observed 25-60 months after renal transplantation. Following a gap of stable cytokine profile (61-120 months), peaks of pro-inflammatory cytokines IL-8, IL-6, IL1ß, TNF-α and IL-12 were observed later on (>120 months) after renal transplantation. Additionally, the categorical analysis of "low" or "high" cytokine producers re-enforce the occurrence of an overall regulatory status early-after stable renal graft function with a predominant pro-inflammatory pattern later on long-term renal transplantation. Taken together, our data suggest that IL-5 is a good biomarker associated with short-term stable renal function, whereas IL-12 seems to be a relevant pro-inflammatory element in long-term renal transplanted patients.

Human parvovirus B19 infection in a renal transplant recipient: a case report.

BACKGROUND: Parvovirus B19 presents tropism for human erythroid progenitor cells, causing chronic anemia in organ transplant recipients, due to their suppressed humoral and cellular responses. Diagnosis may be achieved through serological tests for detection of anti-B19 antibodies. However, renal transplant recipients are not routinely tested for parvovirus B19 infection, since there is scanty data or consensus on screening for B19 infection, as well as for treatment or preventive management of transplanted patients. CASE PRESENTATION: Herein we report a kidney transplant recipient, who was unresponsive to treatment of severe anemia, and presented hypocellular hematopoietic marrow, megaloblastosis and hypoplasia of erythroid lineage with larger cells with clear nuclei chromatin and eosinophilic nuclear inclusions. This patient was seropositive for Epstein-Barr and Cytomegalovirus infections and negative for anti-parvovirus B19 IgM and IgG antibodies, although symptoms were suggestive of parvoviruses infection. A qualitative polymerase chain reaction testing for B19 in serum sample revealed positive results for B19 virus DNA. CONCLUSION: This case report suggests that the diagnostic process for parvovirus B19 in renal transplant recipients should include a polymerase chain reaction assay to detect B19-DNA, since specific serological tests may be unreliable given their impaired humoral responses. These results also indicate the importance of considering parvovirus B19 infection in the differential diagnosis of persistent anemia in transplanted patients.

Arranjo matricial e o desafio da interdisciplinaridade na atenção básica: a experiência do Nasf em Camaragibe/PE / Matrix arrangement and the challenge of interdisciplinary primary care: the experience of the NASF in CamaragibelPE, Brazil

Por sentir a necessidade de fortalecer a atenção básica e para aumentar a resolutividade foi que o município de Camaragibe implantou os Núcleos de Apoio à Saúde da Família (NASFs), com base na estratégia de arranjo matricial. Este relato de experiência descreve o desenvolvimento do processo de trabalho do NASF. Definiram-se prioridades de atuação como: educação permanente, por meio da discussão de casos em equipe e dos atendimentos compartilhados, a realização de atividades educativas junto à comunidade, buscando ampliar ações de promoção e prevenção à saúde. Como eixo transversal das atividades, priorizou-se as ações interdisciplinares, sejam nas visitas domiciliares, nas atividades coletivas, nas quais se busca interações de saberes, que se ampliam, se transformam, buscando em cada ação uma oportunidade para construção da integralidade.

Feeling the need to strengthen primary care by increasing resolvability, Camaragibe deployed the Family Health Support Groups (NASFs) based on a matrix arrangement. This report of the experience describes how the work process developed. Priorities for action were defined, such as continuous education by means of team discussions regarding cases and shared care, educational activities in the community with the aim of amplifying health promotion and disease prevention actions. As the transverse axis ofthe activities, interdisciplinary actions were prioritized, either by home visits or group activities, seeking knowledge interaction which is magnified and transformed, in an attempt to build comprehensive actions.

Linfoistiocitose hematofagocítica em transplante renal: relato de caso e revisäo da literatura / Histiocytosis-non-Langerhans-cell in kidney transplantation: case report and literature review

A linfoistiocitose hematogocítica (LH) constitui uma síndrome clínico-patológica associada à febre pancitopenia severa, disfunçäo hepática e distúrbio da coagulaçäo, com hematofagocitose no nível da medula óssea e órgäos linfóides. Ocorre em pacientes imunossuprimidos, sendo induzida por infecçöes bacterianas, viróticas, fúngicas e parasitárias, bem como neoplasias, especialmente os linfomas de células T. Este trabalho relata o primeiro caso do nosso conhecimento de LH em transplante renal no Brasil, discutindo-se a etiologia, fisiopatogenia, manifestaçoös clínicas e tratamento da doença.

Induçäo com doses baixas de OKT3 versus imunossupressäo tríplice em transplante renal com doador cadáver / Induction with low OKT3 dose versus triplex immunossupression in kidney transplantation with cadaver donor

Foram analisados durante um ano, através de um estudo de coorte, dois esquemas de imunossupressäo profilática utilizados em 56 transplantes renais consecutivos de doador cadáver. Trinta e três pacientes receberam induçäo com doses baixas de Orthoclone OKT3 durante 14 dias, associado a ciclosporina A (no 12§ dia), azatioprina e prednisona (grupo OKT3). Vinte e três pacientes foram submetidos a imunossupressäo convencional tríplice (grupo tríplice), que consistiu de ciclosporina A, azatioprina e prednisona, iniciados no dia do transplante. O grupo OKT3 apresentou um retardo no aparecimento do primeiro episódio de rejeiçäo (15,9 vs 6,5 dias), bem como um menor número de rejeiçöes durante o uso do medicamento (27,3 por cento vs 73,9 por cento) e no primeiro mês (42,4 por cento vs 73,9 por cento), mostrando uma tendência para melhor sobrevida do enxerto no primeiro ano de transplante (84 por cento vs 65 por cento). A sobrevida do paciente, incidência de infecçöes, duraçäo da funçäo retardada do enxerto e nível de creatinina foi semelhante em ambos os grupos. A prevalência de citomegalovirus foi de 6,0 por cento (grupo OKT3) e 8,6 por cento (grupo tríplice). Reaçöes colaterais associadas com doses baixas de OKT3 foram frequentes, porém sem repercusäo clínica importante. Concluimos que a induçäo com doses baixas de OKT3 reduz a incidência de rejeiçöes no primeiro mês de transplante, retarda o aparecimento do primeiro episódio de rejeiçäo e mostra uma tendência para melhor sobrevida do enxerto após um ano, reduzindo o custo do tratamento.