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In this study of three strategies — hypothermia, machine perfusion, or both — for pretransplantation preservation of kidneys from brain-dead donors, hypothermia was found to be inferior to machine perfusion.

IntroductionEx vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice.Methods and analysisThis is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020.Trial registration numberISRCTN15821205; Pre-results.

This study explores the impact of using kidneys from very-aged donors to address the organ shortage, focusing on risk factors for graft loss and delayed graft function (DGF), independent of recipient factors. Data were sourced from the French multicentric prospective DIVAT cohort and retrospectively analyzed. The study included adult recipients transplanted between 2007 and 2018 receiving kidneys from brain-deceased donors over 70. The primary endpoint was death-censored graft survival, and secondary endpoint DGF. Among 1036 patients with a median follow-up of 3.96 years (2.01–6.31), donor hypertension (HR 1.46 95% CI (1.09–1.95), cold ischemia time (HR 1.03 per hour 95% CI (1.01–1.06) and HLA mismatches (after adjustment on DGF, HR 1.98 (1.45–2.71)) were significant risk factors for graft loss. Considering DGF, donor serum creatinine (HR 1.01 95% CI (1.01–1.01) per μmol/L), warm and cold ischemia times (HR 1.01 95% CI (1.0–1.01) per minute and HR 1.05 95% CI (1.02–1.08) per hour) and the use of SCOT preservation solution (HR 3.90 95% CI (1.26–11.84)) were deleterious, while hypothermic perfusion machine was protective (HR 0.65 95% CI (0.43–0.99)). The findings emphasize the paucity of modifiable variables associated with long-term outcomes in very-aged donors and the need for peri-transplant preservation strategies.

Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Background Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. Methods BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Discussion If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12617000358347 . Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488 . Registered on 4 February 2019.

Background Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. Methods The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg −1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size ( n  = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). Discussion Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. Trial registration ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016. 

Delayed graft function (DGF) is commonly considered a risk factor for acute rejection, although this finding has not been uniformly observed across all studies. The link between DGF and acute rejection may have changed over time due to advances in immunosuppression and medical management. Here we conducted a cohort study of 645 patients over 12 years to evaluate the association of DGF and biopsy-proven acute rejection (BPAR) in a modern cohort of kidney transplant recipients. DGF was defined as the need for at least one dialysis session in the first week after kidney transplantation. The 1-, 3-, and 5-year cumulative probabilities of BPAR were 16.0, 21.8, and 22.6% in the DGF group, significantly different from the 10.1, 12.4, and 15.7% in the non-DGF group. In multivariable Cox proportional hazards model, the adjusted relative hazard for BPAR in DGF (vs. no DGF) was 1.55 (95% confidence interval (CI): 1.03, 2.32). This association was generally robust to different definitions of DGF. The relative hazard was also similarly elevated for T-cell- or antibody-mediated BPAR (1.52 (0.92, 2.51) and 1.54 (0.85, 2.77), respectively). Finally, the association was consistent across clinically relevant subgroups. Thus DGF remains an important risk factor for BPAR in a contemporary cohort of kidney transplant recipients. Interventions to reduce the risk of DGF and/or its aftereffects remain of paramount importance to improve kidney transplant outcomes.

In as many as 50% of cases the immediate post-kidney transplant course is complicated by delayed graft function that is most commonly related to ischemia and reperfusion injury. In addition to the acute complications related to renal failure and the associated economic impact of prolonged hospitalization, the development of delayed graft function is associated with an increased risk of chronic allograft nephropathy and shortened allograft survival. Challenges in understanding its mechanisms include the complexity, as contributors are derived from both the donor and the recipient. This acute kidney injury is modulated and caused by a complex interplay of events that lead to hypoxic and ischemic injury as well as to altered repair mechanisms. New therapies primarily seek to suppress the inflammatory homing of adaptive immune cells to the kidney, limit cell death, and/or interrupt detrimental signaling of necrosis. Although there are several promising novel targets and innovative therapeutics available, many challenges remain in their translation from bench to bedside. Identifying organs at risk and clearly defined end points will be critical in designing interventional trials.

Adequate intravascular volume maintenance is essential to ensure early graft function during renal transplantation. Various recommendations on optimum fluid therapy are based, at best, on sparse evidence, and that too only from observational studies. This prospective randomized controlled study was done to evaluate the effect of 20 % human albumin on the early graft function in living donor renal transplantation. Eighty patients undergoing renal transplantation were randomly assigned to one of the intraoperative fluid regimens, 0.9 % normal saline with 20 % human albumin (albumin group) or 0.9 % normal saline alone (saline group), after confirming the exclusion criteria. Intravenous fluid infusion was given to keep central venous pressure (CVP) between 12 to 15 mm Hg. The statistical package of social sciences, SPSS version 12, was used for statistical analysis. The intraoperative fluid volume infused [albumin group - 3381 ± 1021.2 vs. saline group - 3487 ± 978.5 (mL)] to maintain target CVP was comparable between the two groups (P value > 0.05). Statistically, no significant difference was found between the two groups in terms of post transplant serum creatinine [day one ; 2.76 ± 1.0 vs. 2.58 ± 0.94, day three ; 1.48 ± 0.53 vs. 1.43 ± 0.71, day seven; 1.42 ± 0.6 vs. 1.42 ± 0.53 (mg / dL)] and urine output [day one; 13122.5 ± 5767.8 vs. 13909.4 ± 5324.7, day three; 9233.9 ± 3267.4 vs. 9250 ± 4794.2, day seven; 7517.6 ± 3043.6 vs. 6921.4 ± 3170 (mL)] (P value >0.05). Postoperative change in body weight [1.89 ± 3.82 vs. 2.48 ± 3.89 (kg)], tissue edema (10% vs. 7.5%), and pulmonary edema (2.5 % vs. 5 %) did not differ significantly (P > 0.05). Twenty percent human albumin given intraoperatively, as a volume expander, does not improve early graft function in living donor renal transplantation. It should be used selectively rather than as a routine protocol.

Background There is increasing need to expand availability of donor liver grafts, including steatotic livers. Steatotic liver is associated with poor outcome post-transplantation but with conflicting results in the literature. The aim of this systematic review was to evaluate the impact of steatotic livers on liver transplantation outcomes. Methods An electronic search of OVID Medline and Embase databases was performed to identify clinical studies that reported outcomes of steatotic livers in liver transplantation. Data were extracted, and basic descriptive statistics were used to summarise data pooled from individual clinical studies. Results Ninety-two articles were identified, of which 34 met the inclusion criteria, and stratified analysis were performed. There was a lack of standardised definition of primary non-function or impaired primary function amongst the studies and description of type of steatosis. Severely (>60 %) steatotic grafts are associated with increased risk of poor graft function, whilst moderate–severe (>30 %) steatotic grafts are associated with decreased graft survival. Conclusions Available evidence showed increased risk of poor graft outcome in moderate–severe steatotic livers. A large prospective multi-centred trial will be required to identify the true risks of steatotic livers. Consistent definition of primary non-function/impaired primary function and description of type of steatosis is also required.