Transplantation
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Graft quality before transplantation is a major factor influencing chronic rejection. Organ preservation and ischemia/reperfusion play an important role in the induction of organ injury. Although both suppression of metabolism by hypothermic preservation and preconditioning before ischemia limit injury, understanding the biochemical signaling pathways will allow us to optimize graft preservation further. ⋯ Pharmacologic activation of AMPK demonstrated its ability to activate endothelial nitric oxide synthase and inhibit nuclear factor-kB, thereby limiting endothelial dysfunction and inflammation. Further, studies in knock-out mice lacking ENTDP1 and NT5E (enzymes catalyzing formation and degradation of AMP, respectively) demonstrated a clear protective role for AMP in ischemia/reperfusion. AMPK activation before or during organ preservation might be a promising pharmacologic approach to limit organ injury and maintain graft quality before transplantation.
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Multicenter Study
Analysis of the lung allocation score estimation of risk of death in patients with pulmonary arterial hypertension using data from the REVEAL Registry.
Waitlist mortality for patients with pulmonary arterial hypertension (PAH) has not improved after implementation of the lung allocation score (LAS). We analyzed data from patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) as a means to compare observed mortality with predicted mortality from the LAS to identify key prognostic parameters that may be incorporated into the LAS to improve waitlist mortality for patients with PAH. ⋯ The LAS is reevaluated every 6 months after the initial 3-year trial period. Our results suggest that an LAS model that includes both 6-MWD and mRAP better discriminates waitlist urgency for patients with PAH than the current LAS.
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This study evaluated the prognostic impact of pretransplant donor-specific anti-human leukocyte antigen antibodies (DSA) detected by single-antigen beads and compared the three generations of crossmatch (XM) tests in kidney transplantation. ⋯ In sensitized recipients, the best prediction of AMR and consecutively reduced graft function is delivered by DSA-I alone at high strength or by DSA-I at low strength in combination with the LXM or CXM.
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BACKGROUND.: We have shown that high-dose intravenous immune globulin (IVIG; 2 g/kg x2 doses)+rituximab (1 g x2 doses) was effective in lowering anti-human leukocyte antigen (HLA) antibodies and improving rates of transplantation. The aim of this report was to evaluate the efficacy of IVIG+rituximab on reduction of anti-HLA antibodies to a level that was permissive for living donor (LD) or deceased donor (DD) transplantation without incurring the risk of antibody-mediated rejection and immediate graft loss. METHODS.: From July 2006 to February 2009, 76 HLA-sensitized (HS) patients who met strict sensitization criteria received kidney transplants after desensitization using IVIG 2 g/kg (days 1 and 30)+rituximab (1 g, day 15). ⋯ The mean serum creatinines, at 12 and 24 months were 1.5+/-1.1 and 1.3+/-0.3 mg/dL, respectively. Viral infections were seen in six patients. CONCLUSIONS.: IVIG and rituximab seems to offer significant benefits in reduction of anti-HLA antibodies allowing improved rates of transplantation for HS patients, especially those awaiting DD, with acceptable antibody-mediated rejection and survival rates at 24 months.
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BACKGROUND.: In kidney transplant, obesity was reported to be associated with increased posttransplant complications and worse survival outcomes. The impact of obesity in simultaneous pancreas-kidney (SPK) transplant is less known. METHODS.: Using Organ Procurement Transplantation Network/United Network for Organ Sharing data as of August 2008, we included all adults (>18 years) type 1 diabetic SPK recipients between years 2000 and 2007 with a pretransplant body mass index (BMI) of 18.5 to 40 kg/m. ⋯ Obesity, but not overweight, was associated with patient death (hazard ratio [HR]: 1.35; 95% CI: 1.00-1.81), pancreas graft loss (HR: 1.41; 95% CI: 1.17-1.69), and kidney graft loss (HR: 1.33; 95% CI: 1.05-1.67) at 3 years. The higher rates of death and graft failure in the first 30 days posttransplant mostly accounted for the 3-year survival differences. CONCLUSION.: Obesity in SPK recipients was associated with increased risk of posttransplant complications, pancreas and kidney graft loss, and patient death.