RESUMO
BACKGROUND: Ischemia-reperfusion induces tubular and endothelial damage in the renal graft and leads to delayed graft function (DGF) and to an early loss of peritubular capillaries (PTC). Few, if any, clinical studies have assessed the impact of proangiogenic and antiangiogenic factors on endothelial repair during renal transplantation (RT)-related ischemia-reperfusion. METHODS: We prospectively assessed the kinetics of the antiangiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) in 136 consecutive RT patients and analyzed sFlt-1 impact on DGF and PTC loss. RESULTS: sFlt-1 plasma levels increased by twofold to threefold throughout the first week after RT. This increase was more marked in recipients of grafts from deceased donors compared with living donors. Patients with DGF had higher sFlt-1 levels at all time points during the first 7 days after RT and a higher peak sFlt-1 compared with those without DGF. In multivariate analysis, a peak plasma sFlt-1 of 250 pg/mL or higher was associated with 2.5-fold increase in the risk of DGF (P=0.04). Similarly, patients with a peak plasma sFlt-1 of 250 pg/mL or higher had a more pronounced early decrease in PTC compared with those with a peak sFlt-1 less than 250 pg/mL. CONCLUSIONS: sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.
Assuntos
Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/epidemiologia , Transplante de Rim/estatística & dados numéricos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Capilares/patologia , Função Retardada do Enxerto/patologia , Feminino , Humanos , Túbulos Renais/irrigação sanguínea , Túbulos Renais/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/epidemiologia , Traumatismo por Reperfusão/patologia , Fatores de Risco , SolubilidadeRESUMO
The number of older patients living with a functioning kidney graft is increasing. However the safety of the immunosuppressive treatment and quality of life in this population have not yet been determined. All patients grafted in France since 1969, born before the January 1 1926 and living with a functioning graft on January 1 2000 were included in this national study including all 34 French transplant centers. Renal function, immunosuppressive treatment, comorbid conditions and quality of life were assessed. From the initial population of 446 patients, 113 (26.2%) were still alive in 2000 (study population). Mean age was 76 yr (range: 74-80) with a mean post-transplant follow-up of 9.9 yr (0.1-28.7). Average serum creatinine level was 129 micromol/L (55-286). Immunosuppression was heterogeneous and included triple therapy (18.6%), dual therapy (41.6%) and monotherapy (40.8%). A history of cancer was noted in 36 of the 113 patients (32.1%) whereas hypertension was the most frequent co-morbid condition (80.3%). Estimated quality of life using the Karnofsky scale was between 80 and 100 in 78.4% of the patients. The immunosuppressive regimen in older renal transplant recipients living with a functioning graft varied widely among the 34 French transplant centers. Renal function in this group of patients was good and quality of life seemed excellent. Cardiovascular disease and malignancies were the main co-morbid conditions.