Death with functioning kidney transplant: an obituarial analysis

Death with a functioning kidney graft (DWFG) is now a major cause of graft loss after renal transplantation, occurring in up to 40% of cases. Its occurrence provides insight into the medical care of subjects with a functioning kidney transplant. In this study, we used the time to DWFG as an endpoint, to test whether improved medical care has contributed to better kidney transplant outcomes. We used single-center data from the Milwaukee Regional Medical Center and Froedtert Hospital, on kidney-only transplants from 1969 through 2005. A total of 3,157 kidney transplants were done at our center during this time. There were 714 deaths with functioning kidney. We also recorded the major causes of DWFG over the time period from 1969 through 2005 divided into 3 epochs. The data were analyzed as a serial collection of yearly obituaries. The time to DWFG has increased to 10 years despite a 20-year increase in the mean age of transplant recipients over the same time period. Better pre-transplant evaluation, improved treatments for hypertension and hyperlipidemia, improved management of acute myocardial infarction, superior immunosuppressive protocols and better prophylaxis and treatment of infectious diseases have all likely contributed to this trend

Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis

The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA. Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations. Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms