RESUMO
Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX(3)C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX(3)CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX(3)CR1, down-modulated CD62L, and increased CD16. In addition, the CD56(dim) natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56(dim)/CD56(bright) ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX(3)CR1(+) leukocytes and the severity of renal failure. Finally, CX(3)CR1(+) leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX(3)CR1(+) cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.
Assuntos
Quimiocinas CX3C/metabolismo , Síndrome Hemolítico-Urêmica/etiologia , Síndrome Hemolítico-Urêmica/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Biópsia , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/patologia , Síndrome Hemolítico-Urêmica/cirurgia , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/citologia , Células Matadoras Naturais/metabolismo , Selectina L/metabolismo , Contagem de Leucócitos , Masculino , Monócitos/metabolismo , Receptores de Quimiocinas/metabolismoRESUMO
Eighteen records from children with renal transplants (RT) and classical haemolytic-uraemic syndrome (HUS) were reviewed. The mean oliguric period was 17.9 +/- 7.5 days; the interval between acute phase and end-stage renal disease (ESRD) was 9.3 +/- 5.2 years. HUS was the most frequent cause of renal transplantation (23.4%). There were no significant differences between patients with HUS and controls (children with RT but without HUS), regarding renal function, frequency of rejections, renal survival (HUS 65%, controls 57%) or patient survival (94.4% and 96.6%, respectively) after 9 years. None had clinical or histopathological evidence of HUS recurrence in the allograft. Of all children with living-related donors (LRD), renal survival after 3 years was longer for those who received cyclosporin A (CSA) (HUS and controls 86%) than for those who did not receive it (HUS 50%, controls 53%). Classical HUS is a frequent cause of ESRD in Argentina. The duration of the acute oliguric period is a good predictor of the likelihood of progression to chronicity. In the classical form of HUS there is no recurrence in the allograft. CSA and LRD can be used without risk in renal transplantation of children with classical HUS.
Assuntos
Síndrome Hemolítico-Urêmica/cirurgia , Transplante de Rim , Criança , Pré-Escolar , Ciclosporina/farmacologia , Feminino , Síndrome Hemolítico-Urêmica/complicações , Humanos , Lactente , Falência Renal Crônica/etiologia , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Sobrevivência de Tecidos , Transplante HomólogoRESUMO
Dois pacientes com síndrome hemolítico-urêmica foram submetidos a transplante renal. Um paciente, portador da forma infantil, recebeu o rim da mäe e evoluiu bem. O outro paciente, com a forma adulta (nefrosclerose pós-parto), teve evoluçäo complexa no pós-transplante, tendo sido nefrectomizado seis semanas após o transplante. O exame histológico do rim transplantado foi compatível com recidiva da nefropatia