MicroRNA-21 (miR-21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation.

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.

Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score for Prediction of Pancreas Transplant Outcomes.

OBJECTIVES: The Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were designed to assist in the evaluation of pancreases for transplant. Preprocurement Pancreas Suitability Score <17 and PancreasDonor Risk Index ≤1.57 were deemed ideal.We aimed to determine the ability ofthese scores to predict pancreas transplant outcomes. MATERIALS AND METHODS: The Pancreas Donor Risk Index and the Preprocurement Pancreas Suitability Score were retrospectively calculated from a prospectively maintained database of consecutive pancreas transplants performed during a 13-year period (December 2004 to November 2017). Outcomes measuredwere rejection rate, graft and patient survival, and duration of hospital stay. RESULTS: Of 159 pancreas transplants (108 simultaneous pancreas and kidney transplants, 33 pancreas after kidney transplants, 18 pancreas-only transplants), full data were available for 155 (97%) to calculate Pancreas Donor Risk Indexes and 129 (81%) to calculate Preprocurement Pancreas Suitability Scores. Fortyseven patients (30%) experienced at least 1 episode of acute rejection. We calculated Pancreas Donor Risk Indexes for 155 patients, and 19 (23%) and 27 (38%) were in the ≤1.57 and >1.57 groups, respectively (P = .047). We calculated Preprocurement Pancreas Suitability Scores for 129 patients, and 12 (21%) and 27 (32%) were in the <17 and ≥17 groups, respectively (P = .202). Donor age and recipientfemale sex were the main predictors forrejection (binary logistic regression, P < .05). One-year graft survival rates were 95% and 81% forthe ≤1.57 and >1.57 PancreasDonor Risk Index groups,respectively, and 95% and 80% forthe <17 and ≥17 Preprocurement Pancreas Suitability Score groups, respectively (not significant). CONCLUSIONS: Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were not helpful to predict graft/patient survival in our population. A higher Pancreas Donor Risk Index was associated with higher risk of graft rejection. Further studies with larger cohorts are required.

Induction with ATG in DCD kidney transplantation; efficacy and relation of dose and cell markers on delayed graft function and renal function.

AIM: We aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy. METHODS: 140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome. RESULTS: Graft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p < 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01). CONCLUSION: Thymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.

Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant: A Randomized Clinical Trial.

Importance: Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). Objective: To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. Design, Setting, and Participants: In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. Interventions: On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Main Outcome and Measures: Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Results: Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Conclusions and Relevance: Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. Trial Registration: isrctn.org Identifier: ISRCTN63852508.

The role of nutritional assessment and early enteral nutrition for combined pancreas and kidney transplant candidates.

BACKGROUND: Early post-operative enteral nutrition is an important part of perioperative management and is strongly supported by ESPEN Guidelines. However, there is limited evidence into the use of Early Enteral Nutrition (EEN) after combined Pancreas and Kidney Transplantation (PKT). We know malnutrition in type-1 diabetics with end stage renal failure (ESRF) is a common problem and a significant risk factor. Therefore, we introduced EEN in our patients. METHOD: We monitored and recorded nutritional data on 29 PKT recipients who underwent transplantation between Oct 2007 and Jan 2010 without a nutritional assessment or EEN [Monitored Group (MG)] and on 30 PKT recipients between Feb 2010 and Dec 2013 who received a nutritional assessment and EEN (Naso-jejunal feed or oral intake with supplementation, according to their nutritional status) [Fed Group (FG)]. The end-point was to assess patients' daily post-transplant nutritional intake. This was calculated as a percentage of estimated nutritional requirements using the Schofield equation with a 25% added stress factor and relevant activity factor. Following a literature search and realistic targets our aim was to reach >60% requirements: achievement of ≥60% energy requirements by day-7 (7d-60%) and at the time of discharge (total-60%) [13,14]. RESULTS: There was no significant difference between MG and FG patients in cold ischemic time (CIT), recipient-age and donor-age, Length of Stay and donor-creatinine. In contrast, FG patients were less frequently in predialysis status 41.4% vs. 26.7%, p = 0.001; and had higher incidence of BMI <22.5 kg/m2 63.3% vs. 48.3%, p = <0.005. In outcomes, FG patients more frequently achieved a higher average % of nutritional requirements in the first week 39.69% vs. 22.37%, p = <0.005; as well as during whole in-patient stay 57.24% vs. 44.43%, p = <0.005 (Table 3, Figs. 1 and 2). The FG spent a greater proportion during the first week 66.7% vs. 31%, p = <0.005; and of whole their admission 93.3% vs. 75.9%, p = <0.005; meeting more than 60% of nutritional requirements. Most important, the need for parenteral nutrition within the FG was significantly lower, 7.1% vs. 20.7%, p < 0.005 (Table 3). CONCLUSION: Our results show that these patients benefit from planned EEN and receive better nutritional support when compared to the patients managed with the historic, reactive approach to nutritional care. Nutritional intake in the first week as well as during the whole admission was superior in patients receiving active EEN despite a more difficult post-operative course due to higher incidence of re-operations compared to the control group. Also the need for parenteral nutrition was significantly lower in this group. In addition, pre-transplant nutritional assessment is beneficial and accurately highlights those who may be at risk of malnutrition pre and post-operatively.

Outcome of pancreas transplantation in recipients older than 50 years: a single-centre experience.

BACKGROUND: Pancreas transplantation (PT) remains the only treatment that can restore insulin independence among insulin-dependent diabetics. An ageing population in developed countries has led to an increasing number of older patients who may be suitable for PT. Some investigators argue that PT in recipients older than 50 years has an inferior outcome compared with the younger group. METHODS: The object of this study was to compare the outcomes of 31 PT in patients aged 50 and above 105 PT in recipients below 50 years performed between June 2001 and December 2007. RESULTS: The incidence of general posttransplant complications were similar in both; 60% in less than 50 vs. 58% in more than or equal to 50, P=0.539. So, as the incidence of other surgical complication in the more than or equal to 50 group compared with less than 50 (graft thrombosis 13% vs. 11.5%; bleeding 19% vs. 6.7%; abdominal abscess 23% vs. 19%; pancreatic leak 13% vs. 9.6%). There was no significant difference in the incidence of urinary tract infection and early rejection in either group. However, the incidence of respiratory tract infection was significantly higher in more than or equal to 50 (38.7% in >or=50 vs. 9.6% in <50, P=0.003). One-year patient survival was 88% in more than or equal to 50 vs. 92% in less than 50 group, P=0.399; and pancreas graft survival rate was similar (79% in the >or=50 and 74% in <50, P=0.399). CONCLUSION: This study demonstrates that it is feasible to safely transplant potential PT recipients aged 50 and above. However, good medical assessment and careful patient selection is strongly recommended.