Expanding the use of expanded criteria donors in kidney transplantation

Although the use of kidney allografts from expanded criteria donors (ECD) has increased in recent years, the reported discard rates are also growing. the influence of ECD characteristics on transplant outcomes is still underevaluated.This retrospective study investigated the influence of preimplantation biopsy findings and delayed graft function (DGF) on patient and graft survivals and renal function at 36 months in a cohort of 372 ECD kidney transplant recipients.Patient and graft survivals were 91.6 and 68.9 %. the incidence of biopsy-proven acute rejection was 31 %. There were no differences in patient (88.6 vs. 91.1 vs. 94.7 vs. 78.6 %, p = 0.10) or graft (78.1 vs. 72.2 vs. 60.5 vs. 62.6 %, p = 0.14) survivals and renal function (41.7 +/- A 25.6 vs. 39.9 +/- A 29.9 vs. 38.1 +/- A 30.6 vs. 37.4 +/- A 29.2 mL/min, p = 0.79) comparing ECD kidneys with mild, moderate, and severe histological changes or with no preimplantation biopsy, respectively. However, severe scored transplants had the worst death-censored graft survival (OR 3.1, 95 % CI 1.4-6.9, p = 0.007). No significant differences in patient (86.2 vs. 83.4 %, p = 0.17) or graft (73.7 vs. 65.9 %, p = 0.06) survivals and renal function (38.9 +/- A 28.6 vs. 39.9 +/- A 28.4 mL/min, p = 0.72) were observed comparing patients with or without DGF. Multivariable analysis found diabetes history as the only independent risk factor for graft loss (OR 2.1, 95 % CI 1.3-3.3, p = 0.003) or patient death (OR 3.1, 95 % CI 1.5-5.8, p < 0.001).Within the limitations of sample size and short follow-up time, in this cohort of ECD kidney transplant recipients the severity of histological changes observed in preimplantation biopsies was independently associated with graft loss.Universidade Federal de São Paulo, Transplant Div, Hosp Rim & Hipertensao, BR-04038002 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim, BR-04038002 São Paulo, BrazilUniversidade Federal de São Paulo, Transplant Div, Hosp Rim & Hipertensao, BR-04038002 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim, BR-04038002 São Paulo, BrazilWeb of Scienc

Elementary tetrahelical protein design for diverse oxidoreductase functions

Emulating functions of natural enzymes in man-made constructs has proven challenging. Here we describe a man-made protein platform that reproduces many of the diverse functions of natural oxidoreductases without importing the complex and obscure interactions common to natural proteins. Our design is founded on an elementary, structurally stable 4-α-helix protein monomer with a minimalist interior malleable enough to accommodate various light- and redox-active cofactors and with an exterior tolerating extensive charge patterning for modulation of redox cofactor potentials and environmental interactions. Despite its modest size, the construct offers several independent domains for functional engineering that targets diverse natural activities, including dioxygen binding and superoxide and peroxide generation, interprotein electron transfer to natural cytochrome c and light-activated intraprotein energy transfer and charge separation approximating the core reactions of photosynthesis, cryptochrome and photolyase. The highly stable, readily expressible and biocompatible characteristics of these open-ended designs promise development of practical in vitro and in vivo applications