Lesão renal aguda e hipertensão arterial em pacientes com Anemia de Fanconi após transplante de células tronco hematopoiéticas

Orientadora: Prof. Dra. Carmem Maria Sales BonfimCoorientador: Prof. Dr. Fellype Carvalho BarretoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Saúde da Criança e do Adolescente. Defesa : Curitiba, 02/12/2020Inclui referências: p. 76-85Resumo: Anemia de Fanconi (AF) é uma doença rara caracterizada por falência de medula óssea (FMO), predisposição ao desenvolvimento de câncer e múltiplos defeitos congênitos, entre eles malformações do rim e do trato urinário (CAKUT). O transplante de células tronco hematopoiéticas (TCTH) é o único tratamento curativo para as condições hematológicas e está associado a complicações como lesão renal aguda (LRA) e hipertensão arterial (HAS). Este estudo retrospectivamente avaliou uma coorte de 107 pacientes com AF, submetidos a TCTH de 2009 a 2017. Foram avaliadas incidência de LRA e HAS, bem como os fatores de risco associados, nos primeiros 100 dias após o TCTH e sua evolução até 2 anos de seguimento. A incidência de LRA foi de 18,7%, predominantemente em estágios iniciais. Os principais fatores de risco para LRA foram idade superior a 11 anos (OR=3,53), infecção e uso concomitante de ? 5 medicações nefrotóxicas (OR-3,53; p=0,015), especialmente inibidores de enzima conversora da angiotensina (IECA) (OR=3,03; p=0,029). HAS foi encontrada em 72% dos pacientes nos primeiros 100 dias, a maioria deles (62,3%) em estágio 2 e houve associação com uso de ciclosporina (CSA). A incidência de CAKUT foi de 33,7% e, embora não tenha sido encontrada associação com LRA, os pacientes com estas malformações apresentaram maior incidência de HAS, bem como menores taxas de filtração glomerular. A baixa incidência de LRA encontrada pode estar associada ao uso de regime de condicionamento de intensidade reduzida. Os episódios foram transitórios e houve recuperação da função renal. A incidência de HAS foi elevada, e sua resolução associou-se à suspensão da CSA. Pacientes com CAKUT apresentaram maior incidência de HAS e menor TFG em todos os momentos avaliados, sugerindo maior susceptibilidade ao desenvolvimento de doença renal crônica. Os resultados deste trabalho apontam para a necessidade da criação de estratégias para proteção e preservação da função renal nestes pacientes, entre elas a avaliação anatômica e funcional minuciosa do trato urinário, a vigilância rigorosa do uso de medicações nefrotóxicas e a monitorização contínua da pressão arterial. Palavras-chave: Anemia de Fanconi. Transplante de células tronco hematopoiéticas. Lesão renal aguda. Hipertensão arterial.Abstract: Fanconi Anemia (FA) is a rare disease characterized by progressive bone marrow failure, cancer predisposition and multiple systemic malformations, including congenital abnormalities of kidney and urinary tract (CAKUT). Hematopoietic stem cell transplantation (HSCT), the only curative treatment for its hematological complications, may be associated with acute kidney injury (AKI) and arterial hypertension. This retrospective study analyzed a cohort of 107 patients with FA, submitted to HSCT between 2009 and 2017. The incidence of AKI and HAS, as well as associated risk factors, were investigated in the first100 days after HSCT and up to 2 years of follow-up. AKI incidence was 18.7%, mostly in early stages. The main risk factors for AKI were age older than 11 years (OR-3.53), infection and the concomitant use of ? 5 nephrotoxic medications (OR=3.53; p=0.015), especially angiotensin converting enzyme inhibitors (OR=3.03; p=0.029). Hypertension was found in 72% of the patients within the first 100 days, most of them (62.3%) stage 2 and was associated with cyclosporine therapy. CAKUT were present in 33.7% of the patients and were associated with both hypertension (86%) and lower kidney function, although no association with AKI was found. The low AKI incidence found may be associated with the reduced conditioning regimen used for these patients. The episodes were transient and renal function was restored. The incidence of hypertension was high, and its resolution was associated with the suspension of cyclosporine. Patients with CAKUT had a higher incidence of hypertension and lower glomerular filtration rate at all study points, suggesting greater susceptibility to the development of chronic kidney disease. This study points out the need for strategies to preserve and/or improve kidney function in these patients, including detailed anatomical and functional urinary tract evaluation, strict surveillance of the use of nephrotoxic medications and continuous monitoring of blood pressure. Keywords: Fanconi anemia. Hematopoietic cell Transplantation. Acute Kidney Injury. Hypertension

Collaborative brazilian pediatric renal transplant registry (CoBrazPed-RTx) : a report from 2004 to 2018

The Brazilian collaborative registry for pediatric renal transplantation began in 2004 as a multicenter initiative aimed at analyzing, reporting, and disseminating the results of pediatric renal transplantation in Brazil. Data from all pediatric renal transplants performed from January 2004 to May 2018 at the 13 participating centers were analyzed. A total of 2744 pediatric renal transplants were performed in the thirteen participating centers. The median age at transplantation was 12.2 years, with the majority being male recipients (56%). The main underlying diseases were CAKUT (40.5%) and glomerulopathy (28%). 1981 (72%) of the grafts were from deceased donors (DD). Graft survival at one year (censored by death) was 94% in the live donor group (LD) and 91% in the DD group (log-rank test P < 0.01). The patient's survival at one and 5 years was 97% and 95% for the LD group and 96% and 93% for the DD group (log-rank test P = 0.02). The graft loss rate was 19% (n = 517), more frequently caused by vascular thrombosis (n = 102) and chronic graft nephropathy (n = 90). DD recipients had 1.6 (1.0-2.2) times greater chance of death and 1.5 (1.2-1.8) times greater chance of graft loss compared to LD recipients. The mortality rate was 5.4% (n = 148), mainly due to infection (n = 69) and cardiovascular disease (n = 28). The results of this collaborative pediatric renal transplant record are comparable to other international registries, although we still have a high infection rate as a cause of death23