The New UK National Kidney Allocation Scheme With Maximized "R4-D4" Kidney Transplants: Better Patient-to-Graft Longevity Matching May Be at the Cost of More Resources.

OBJECTIVES: A new kidney matching scheme for allocation of deceased donor kidneys for transplantation was introduced in the United Kingdom in September 2019. Donors and recipients are stratified into quartiles derived from demographic and retrieval indices associated with risk of adverse outcome. We present data on 2 years of transplants, with the aim of understanding the potential impacts ofthe scheme on patient/transplant outcomes, hospitalization, and resource utilization. MATERIALS AND METHODS: All deceased donortransplants from 2015 and 2016 were reclassified using the risk quartiles (D1-D4 for donor and R1-R4 for recipient, where 4 is highestrisk). Inpatientlength of stay, kidney function defined by estimated glomerular rate at 1 year, and patient survival data were collected. RESULTS: Of the 195 deceased donor transplants analyzed, 144 recipients (73.4%) were in the highest risk R4 category, including 55 with R4-D4 combination (28.1%). Recipients in the R4 category had longer index admissions (mean of 12.4 vs 8.1 days for R1-R3; P = .002) and higher subsequent admission rates 90 days posttransplant(185.7 vs 122.7/1000 patient days for R1-R3; P < .001). Kidney transplant function at 1 year was lower for grafts categorized as D4 (mean estimated glomerular filtration rate of 35.7 vs 54.8 mL/min/1.73 m2 for D1-D3; P < .001). However, survival for R4 recipients with D4 kidneys was not significantly differentfrom R4 recipients with D1 to D3 kidneys (4-year patient survival rate with R4-D4 combination was 90.9%). CONCLUSIONS: The principles ofthe allocation scheme in matching graft and patient survival were already largely being observed (matching higher risk deceased donor kidneys to higher risk recipients). However, an increase in D4 proportions in the R4 group may be associated with longer hospitalization posttransplant. Consideration should be given to mitigation strategies to address this. Despite poorer graft function, patient survival appears satisfactory.

Transplantation of kidneys after normothermic perfusion: A single center experience.

BACKGROUND: In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP. METHODS: Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). RESULTS: Six-hundred and thirty-two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One-year graft loss rate was 3.4% for NRP and 6.0% for standard DCD. CONCLUSION: This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.

Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy.

The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.

SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: A national cohort study.

Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory-confirmed SARS-CoV-2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow-up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case-mix. One hundred ninety-seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS-CoV-2. Mortality after testing positive for SARS-CoV-2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS-CoV-2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS-CoV-2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.

A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary Immunosuppression following Non-Heart Beating Donor Kidney Transplantation.

INTRODUCTION: With calcineurin inhibitors potentiating damage from ischaemia-reperfusion injury in kidneys from donors after cardiac death we wanted to investigate the role of substituting sirolimus for tacrolimus in the delayed introduction of calcineurin inhibitor regime used in our centre. METHOD: A prospective randomised paired open-label study was performed taking pairs of kidneys from each donor and randomising one to a tacrolimus-based regime and the other to a similar regime based on sirolimus. Graft function at one year was the primary endpoint. RESULTS: Total 31 pairs of kidneys were randomised to each group, with 19 pairs of recipients available for analysis after post-randomisation study exclusions. Despite a higher incidence of biopsy proven acute rejection in the sirolimus group, renal allograft function was similar in both groups at three-monthly intervals up to one year post-transplant. All episodes of acute rejection in the sirolimus group occurred in the first three months. Graft and patient survival at one year was 100% in the tacrolimus group, with one death with functioning graft in the sirolimus group (95% survival). Unfortunately, 10 of the 19 patients in the sirolimus arm required switch of medication to tacrolimus due to acute rejection or intolerable drug side effects. CONCLUSIONS: Graft survival and function were very similar in the two groups despite the higher rate of acute rejection in the sirolimus arm, raising the possibility that the damage done by acute rejection was adequately offset by the nephron-sparing effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer-term maintenance immunosuppressant after initial treatment with a different agent such as tacrolimus or belatacept.

Successful endovascular salvage of a pancreatic graft after a venous thrombosis: case report and literature review.

Simultaneous kidney and pancreatic transplant is the criterion standard for treatment of end-stage renal failure because of diabetic nephropathy. Venous thrombosis occurs in approximately 5% of pancreatic transplants, and it is notoriously difficult to treat, forming the most common nonimmunologic cause of graft loss. We report a case of early detection of pancreatic graft venous thrombosis by measuring urinary amylase, resulting in the successful endovascular salvage of the pancreatic graft.

The effect of inadequate in situ perfusion in the non heart-beating donor.

In situ aortic perfusion in the nonheart-beating donors (NHBD) is an important procedure to reduce primary warm ischaemic injury prior to formal donor organ retrieval. It allows an interim period to obtain donor family consent and theatre preparation. This study describes our experience of inadequate aortic perfusions resulting from difficult aortic cannulations and associated adverse outcome despite reasonable viability tests. Since 1998, all NHBD in our institution are perfused in situ using a double balloon triple lumen (DBTL) catheter inserted through a femoral artery cut-down procedure. The DBTL catheter is positioned with distal occlusive balloon at the aortic bifurcation using the "pull-back" technique, the proximal occlusive balloon lies above the renal arteries. This provides selective aortic perfusion in particular the kidneys. Venous decompression using a femoral vein catheter enables a "two-way infusion system". Pre-transplant viability status of retrieved kidneys is determined by measuring pressure/resistance characteristics to the flow and biochemical markers for ischaemic injury. There were 90 NHBD renal transplants performed from 72 donors. Three renal transplants were carried out from three donors of ineffective in situ perfusion secondary to cannulation difficulties. Femoral cannulation was difficult as a result of extensive atherosclerosis of donor vessels. The comparison of allograft outcome from effective and ineffective in situ perfusion of donors showed high rate of primary nonfunction (PNF) from ineffective perfusion (chi-squared, P < 0.0001). The cases demonstrated poor outcome from ineffective perfusion related to the cannulation difficulties. Therefore a strict policy should be taken in cases where aortic cannulation and perfusion is inadequate, despite pretransplant assessment. In these circumstances, the primary warm ischaemia time should be extended to include this period of ineffective perfusion.

Dual ipsilateral renal transplantation from a non-heart-beating donor.

A case is described where both kidneys from non-heart-beating (expanded criteria) donors were dual transplanted ipsilaterally. Although both kidneys passed viability tests on the Newcastle machine preservation system and biomarkers' evaluation, there were logistical issues where the cold ischaemic time was too protracted necessitating the transplantation of both kidneys into one recipient. The recipient had satisfactory outcome with the Cockcroft-Gault creatinine clearance of 72.47 (36.29 ml/min individual kidney glomerular filtration rate) suggesting beneficial use of sub-optimal organs to improve outcome.

Graft function after kidney transplantation from non-heartbeating donors according to maastricht category.

PURPOSE: Donor shortages have led to some groups using alternative sources such as non-heartbeating donors (NHBDs). Kidneys from NHBDs suffer from warm ischemia at cardiac arrest which is reflected by acute tubular necrosis of the allograft, resulting in a period of delayed graft function. NHBDs are categorized by the circumstances surrounding the agonal events of death which reflect differences in the likelihood of ischemic injury to the kidney. In this study we determined the impact of ischemic injury on the renal function of kidneys procured from different categories of NHBDs. MATERIALS AND METHODS: From 1998 to 2003, 144 kidneys were procured from 72 NHBDs resulting in 93 transplants characterized into Maastricht categories II, III and IV NHBD renal transplants. Renal function after transplant was evaluated from the last dialysis until discharge from hospital, and then at 3 monthly intervals thereafter. RESULTS: Primary warm ischemic time is more prolonged in the uncontrolled donor (category II) than controlled donor (category III greater than IV). Delayed graft function occurs more frequently (Maastricht category II 83.8%, III 67.4% and IV 0%, ANOVA p <0.05) and the return to normal function is more prolonged in uncontrolled donors. This is illustrated by the greater incidence of acute tubular necrosis (Maastricht category II 81.1%, III 65.2% and IV 50.0%, ANOVA p = nonsignificant) in the kidney allograft. There was no difference in year 1 allograft survival (Maastricht category II 83.9%, III 92.5% and IV 100%, ANOVA p = nonsignificant). CONCLUSIONS: Early graft function is poorest in kidneys derived from Maastricht category II donors and best in category IV with III in-between. However, after 3 months the function of kidneys from all donors is the same.

Transplantation from non heart beating donors in Newcastle upon Tyne.

Donor shortage has led transplant surgeons to reevaluate the concept of non heart beating donation. Organs from such donors are exposed to anoxia prior to harvesting and a portion of them will consequently present with delayed graft function. There is a need for dependable viability testing of organs from less than ideal NHBD donors and machine perfusion of kidneys provides such a tool. Our experience with own design machine perfusion device, studied parameters, perfusion solutions and outcomes is presented. Emphasis is placed on the incomparability of results obtained from different perfusion systems and the need to establish local criteria of kidney viability.