Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.

Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R.

Ureteral stent placement and BK viremia in kidney transplant recipients.

INTRODUCTION: BK virus (BKV) infection is an important cause of kidney transplant dysfunction. A possible association of double-J ureteral stent placement and BK viremia has been suggested in previous studies; however, risk factors for BK are incompletely understood. We aimed to determine if stent placement is an independent risk factor for BK viremia. METHODS: Data were collected on consecutive kidney-only transplant recipients between December 1, 2006 and June 30, 2010. All patients had at least 12 months of follow-up. RESULTS: Of 600 consecutive kidney transplants, BK viremia within the first post-transplant year was detected in 93 patients (15.5%); in 70 of these cases, the peak BKV polymerase chain reaction was ≥10,000 copies/mL. By multivariate analysis, significant risk factors for BK viremia were recipient age (P = 0.02) and stent placement (P = 0.03). Stents were placed in 49.2% and removed at a median of 46 days (range: 11-284) post transplantation; removals occurred within 0-30, 30-60, 60-90, 90-120, 120-150, and >150 days post transplantation in 18.4%, 67.2%, 10.5%, 2.4%, 1.0%, and 0.3% of cases, respectively. No association was found of BK viremia with stent duration >46 days (P = 0.70) or by the 6-level groupings (P = 0.92). CONCLUSIONS: Although we observed a significant association of BK viremia with stent placement, no dose-dependent effect was seen.

Impact of cold ischemia time on graft survival among ECD transplant recipients: a paired kidney analysis.

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17,514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14,230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥ 15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1-3 h (p = 0.90), 4-9 h (p = 0.41), 10-14 h (p = 0.36) or ≥ 15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Successful treatment of invasive mucormycosis in a liver transplant patient by arm amputation.

Mucormycosis is an uncommon but frequently fatal infectious complication after solid organ transplantation. We describe successful treatment of invasive mucormycosis in a liver transplant recipient by wound debridement, a right above-elbow arm amputation, and antifungal medications. Early recognition, prompt operative intervention, and initiation of an appropriate antifungal treatment are very important in the management of mucormycosis, a potentially life-threatening infection.

Recovery factors affecting utilization of small pediatric donor kidneys.

UNLABELLED: Kidneys from small pediatric donors are underutilized. Using data from the Scientific Registry of Transplant Recipients for donors <21 kg in which at least one organ was recovered from 1997 to 2007 (n = 3341), donor and recovery factors were evaluated by multivariate analysis for associations with (a) kidney nonrecovery and (b) transplantation of recovered kidneys. RESULTS: The proportion of kidney recoveries were 55% during liver procurements and 40% during intestine procurements amongst donors <10 kg (p < 0.01) compared to 93% and 88%, respectively, for donors weighing 10-20 kg (p = 0.003). Intestine procurement was independently associated with an 81% greater likelihood of kidney nonrecovery (p < 0.0001) and a 48% lower likelihood of transplantation (p = 0.0004). A multivariate Cox model indicated that single kidney recipients had a 63% higher risk of graft failure compared with en bloc kidney recipients (p < 0.0001); however, concurrent intestine recovery was not a significant risk factor for graft loss. Intestine recovery from donors <21 kg of age is strongly associated with higher kidney nonrecovery and lower transplantation rates. Graft survival is worse with single kidney transplantation, but is not significantly affected by intestine recovery. Small pediatric donors procurement teams should strive to increase kidney recoveries overall and en bloc recoveries in particular.