Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30‐kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24‐h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short‐term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.     

Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage—Brief,Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?

Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days’ follow‐up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts.     

Laparoscopic sleeve gastrectomy improves renal transplant candidacy and posttransplant outcomes in morbidly obese patients

Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new‐onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single‐center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011‐2016 (n = 20). Post‐LSG kidney recipients were compared with similar‐BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed‐rank test were used to compare groups. Among post‐LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m² at initial encounter, which decreased to 32.3 ± 2.9 kg/m² prior to transplantation (P < .01). No complications, readmissions, or mortality occurred following LSG. After transplantation, one patient (5%) experienced DGF, and no patients experienced NODAT. Allograft and patient survival at 1‐year posttransplantation was 100%. Compared with non‐LSG patients, post‐LSG recipients had lower rates of DGF (5% vs 20%) and renal dysfunction–related readmissions (10% vs 27.5%) (P < .05 each). Perioperative complications, allograft survival, and patient survival were similar between groups. These data suggest that morbidly obese patients with end‐stage renal disease who undergo LSG to improve transplant candidacy, achieve excellent posttransplantation outcomes.     

Impact of ureteral stricture and treatment choice on long‐term graft survival in kidney transplantation

We aimed to evaluate the influence of urological complications occurring within the first year after kidney transplantation on long‐term patient and graft outcomes, and sought to examine the impact of the management approach of ureteral strictures on long‐term graft function. We collected data on urological complications occurring within the first year posttransplant. Graft survivals, patient survival, and rejection rates were compared between recipients with and without urological complications. Male gender of the recipient, delayed graft function, and donor age were found to be significant risk factors for urological complications after kidney transplantation (P < .05). Death censored graft survival analysis showed that only ureteral strictures had a negative impact on long‐term graft survival (P = .0009) compared to other complications. Death censored graft survival was significantly shorter in kidney recipients managed initially with minimally invasive approach when compared to the recipients with no stricture (P = .001). However, graft survival was not statistically different in patients managed initially with open surgery (P = .47). Ureteral strictures following kidney transplantation appear to be strongly negatively correlated with long‐term graft survival. Our analysis suggests that kidney recipients with ureteral stricture should be managed initially with open surgery, with better long‐term graft survival.     

Hospital readmissions following HLA‐incompatible live donor kidney transplantation: A multi‐center study

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor‐specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22‐center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant‐matched controls and to waitlist‐only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed‐effects Poisson regression. In the first month, ILDKTs had a 1.28‐fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13‐1.46; P < .001). Risk peaked at 6‐12 months (relative risk [RR] 1.67, 95% CI 1.49‐1.87; P < .001), attenuating by 24‐36 months (RR 1.24, 95% CI 1.10‐1.40; P < .001). ILDKTs had a 5.86‐fold higher readmission risk (95% CI 4.96‐6.92; P < .001) in the first month compared to waitlist‐only controls. At 12‐24 (RR 0.85, 95% CI 0.77‐0.95; P = .002) and 24‐36 months (RR 0.74, 95% CI 0.66‐0.84; P < .001), ILDKTs had a lower risk than waitlist‐only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist‐only controls should be considered in regulatory/payment schemas and planning clinical care.     

Early graft function and intrarenal resistant index after kidney transplantation using Biolasol—A new solid organ preservation fluid

Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin—UW, Institute Georges Lopez—IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3 mg/dL—immediate graft function, IGF or >3 mg/dL—slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P < .05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.     

Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart‐beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30′), 70 minutes (DCD70′), and 120 minutes (DCD120′) of warm ischemia were studied. The HBD, DCD30′, and DCD70′‐groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120′‐group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120′‐group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold‐urea increase was significantly lower in the DCD120′‐group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120′‐group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120′‐group (≤1) (P < .01). Three hours after transplantation, the DCD120′‐group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time‐points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.     

Outcomes of en bloc simultaneous liver‐kidney transplantation compared to the traditional technique

Simultaneous liver‐kidney transplantation (SLKT) is indicated for patients with end‐stage liver disease (ESLD) and concurrent renal insufficiency. En bloc SLKT is an alternative to traditional separate implantations, but studies comparing the two techniques are limited. The en bloc technique maintains renal outflow via donor infrahepatic vena cava and inflow via anastomosis of donor renal artery to donor splenic artery. Comparison of recipients of en bloc (n = 17) vs traditional (n = 17) SLKT between 2013 and 2017 was performed. Recipient demographics and comorbidities were similar. More recipients of traditional SLKT were dialysis dependent (82.4% vs 41.2%, P = .01) with lower baseline pretransplant eGFR (14 vs 18, P = .01). En bloc SLKT was associated with shorter kidney cold ischemia time (341 vs 533 minutes, P < .01) and operative time (374 vs 511 minutes, P < .01). Two en bloc patients underwent reoperation for kidney allograft inflow issues due to kinking and renal steal. Early kidney allograft dysfunction (23.5% in both groups), 1‐year kidney graft survival (88.2% vs 82.4%, P = 1.0), and posttransplantation eGFR were similar between groups. In our experience, the en bloc SLKT technique is safe and feasible, with comparable outcomes to the traditional method.     

The “oldest and coldest” shipped living donor kidneys transplanted through kidney paired donation

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation (“oldest kidneys”) and prolonged cold ischemia time (“coldest kidneys”) on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death‐censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.     

Outcomes of organ transplants when the donor is a prior recipient

Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donation After Transplant (ODAT) donors. We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From October 1, 1987 to June 30, 2015, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately 4 years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period June 1, 2005 to December 31, 2014, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non‐ODAT liver transplants (P = .008). Kidney grafts donated by ODAT donors whose initial transplant occurred >1 year prior were associated with significantly increased graft failure (P = .012). Despite increased risk of graft failure amongst certain ODAT grafts, 5‐year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances.     

Using computer‐assisted morphometrics of 5‐year biopsies to identify biomarkers of late renal allograft loss

The current Banff scoring system was not developed to predict graft loss and may not be ideal for use in clinical trials aimed at improving allograft survival. We hypothesized that scoring histologic features of digitized renal allograft biopsies using a continuous, more objective, computer‐assisted morphometric (CAM) system might be more predictive of graft loss. We performed a nested case‐control study in kidney transplant recipients with a surveillance biopsy obtained 5 years after transplantation. Patients that developed death‐censored graft loss (n = 67) were 2:1 matched on age, gender, and follow‐up time to controls with surviving grafts (n = 134). The risk of graft loss was compared between CAM‐based models vs a model based on Banff scores. Both Banff and CAM identified chronic lesions associated with graft loss (chronic glomerulopathy, arteriolar hyalinosis, and mesangial expansion). However, the CAM‐based models predicted graft loss better than the Banff‐based model, both overall (c‐statistic 0.754 vs 0.705, P < .001), and in biopsies without chronic glomerulopathy (c‐statistic 0.738 vs 0.661, P < .001) where it identified more features predictive of graft loss (% luminal stenosis and % mesangial expansion). Using 5‐year renal allograft surveillance biopsies, CAM‐based models predict graft loss better than Banff models and might be developed into biomarkers for future clinical trials.     

Organ‐specific metabolic profiles of the liver and kidney during brain death and afterwards during normothermic machine perfusion of the kidney

We investigated metabolic changes during brain death (BD) using hyperpolarized magnetic resonance (MR) spectroscopy and ex vivo graft glucose metabolism during normothermic isolated perfused kidney (IPK) machine perfusion. BD was induced in mechanically ventilated rats by inflation of an epidurally placed catheter; sham‐operated rats served as controls. Hyperpolarized [1‐¹³C]pyruvate MR spectroscopy was performed to quantify pyruvate metabolism in the liver and kidneys at 3 time points during BD, preceded by injecting hyperpolarized[1‐¹³C]pyruvate. Following BD, glucose oxidation was measured using tritium‐labeled glucose (d ‐6‐3H‐glucose) during IPK reperfusion. Quantitative polymerase chain reaction and biochemistry were performed on tissue/plasma. Immediately following BD induction, lactate increased in both organs (liver: eµ_d0.21, 95% confidence interval [CI] [?0.27, ?0.15]; kidney: eµ_d0.26, 95% CI [?0.40, ?0.12]. After 4 hours of BD, alanine production decreased in the kidney (eµ_d0.14, 95% CI [0.03, 0.25], P < .05). Hepatic lactate and alanine profiles were significantly different throughout the experiment between groups (P < .01). During IPK perfusion, renal glucose oxidation was reduced following BD vs sham animals (eµ_d0.012, 95% CI [0.004, 0.03], P < .001). No differences in enzyme activities were found. Renal gene expression of lactate‐transporter MCT4 increased following BD (P < .01). In conclusion, metabolic processes during BD can be visualized in vivo using hyperpolarized magnetic resonance imaging and with glucose oxidation during ex vivo renal machine perfusion. These techniques can detect differences in the metabolic profiles of the liver and kidney following BD.     

Outcomes of donation after circulatory death kidneys undergoing hypothermic machine perfusion following static cold storage: A UK population‐based cohort study

Evidence is currently lacking regarding the outcomes of kidneys undergoing hypothermic machine perfusion (HMP) in patients in the United Kingdom. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single‐organ donation after circulatory death (DCD) kidneys preserved with HMP with those preserved using only static cold storage (SCS). Between 2007 and 2015, HMP was used in 19.1% (864/4,529) of kidneys. Rates of delayed graft function (DGF) were significantly lower in organs preserved with HMP than for organs preserved with SCS (34.2% vs 42.0%, P < .001), despite a slightly longer cold ischemic time (median: 14.8 vs 14.1 hours, P < .001). Multivariable analysis found the effect of preservation modality to remain significant, with HMP organs having a significantly lower rate of DGF (odds ratio 0.65, 95% confidence interval 0.53‐0.80, P < .001) and significantly shorter times to DGF resolution (average: 6.1 vs 7.4 days, P = .003) than SCS organs. The patient (P = .313) and graft (P = .263) survival rates were similar in the 2 preservation groups. HMP was associated with a marginal functional benefit in 1‐year creatinine values (P = .044), with adjusted averages of 1.36 mg/dL (HMP) versus 1.40 mg/dL (SCS). This study supports the use of HMP and aids decision‐making over its instigation, which may improve short‐term patient outcomes.     

Outcomes of kidney retransplantation after graft loss as a result of BK virus nephropathy in the era of newer immunosuppressant agents

We conducted this study using the updated 2005‐2016 Organ Procurement and Transplantation Network database to assess clinical outcomes of retransplant after allograft loss as a result of BK virus–associated nephropathy (BKVAN). Three hundred forty‐one patients had first graft failure as a result of BKVAN, whereas 13 260 had first graft failure as a result of other causes. At median follow‐up time of 4.70 years after the second kidney transplant, death‐censored graft survival at 5 years for the second renal allograft was 90.6% for the BK group and 83.9% for the non‐BK group. In adjusted analysis, there was no difference in death‐censored graft survival (P = .11), acute rejection (P = .49), and patient survival (P = .13) between the 2 groups. When we further compared death‐censored graft survival among the specific causes for first graft failure, the BK group had better graft survival than patients who had prior allograft failure as a result of acute rejection (P < .001) or disease recurrence (P = .003), but survival was similar to those with chronic allograft nephropathy (P = .06) and other causes (P = .05). The better allograft survival in the BK group over acute rejection and disease recurrence remained after adjusting for potential confounders. History of allograft loss as a result of BKVAN should not be a contraindication to retransplant among candidates who are otherwise acceptable.     

The impact of postreperfusion syndrome during liver transplantation using livers with significant macrosteatosis

The impact of postreperfusion syndrome (PRS) during liver transplantation (LT) using donor livers with significant macrosteatosis is largely unknown. Clinical outcomes of all patients undergoing LT with donor livers with moderate macrosteatosis (30%‐60%) (N = 96) between 2000 and 2017 were compared to propensity score matched cohorts of patients undergoing LT with donor livers with mild macrosteatosis (10%‐29%) (N = 96) and no steatosis (N = 96). Cardiac arrest at the time of reperfusion was seen in eight (8.3%) of the patients in the moderate macrosteatosis group compared to one (1.0%) of the patients in the mild macrosteatosis group (P = .02) and zero (0%) of the patients in the no steatosis group (P = .004). Patients in the moderate macrosteatosis group had a higher rate of PRS (37.5% vs 18.8%; P = .004), early allograft dysfunction (EAD) (76.4% vs 25.8%; P < .001), renal dysfunction requiring continuous renal replacement therapy following transplant (18.8% vs 8.3%; P = .03) and return to the OR within 30 days (24.0% vs 7.3%; P = .002), than the no steatosis group. Both long‐term patient (P = .30 and P = .08) and graft survival (P = .15 and P = .12) were not statistically when comparing the moderate macrosteatosis group to the mild macrosteatosis and no steatosis groups. Recipients of LT using livers with moderate macrosteatosis are at a significant increased risk of PRS. If patients are able to overcome the initial increased perioperative risk of using these donor livers, long‐term graft survival does not appear to be different than matched recipients receiving grafts with no steatosis.     

BMX‐001, a novel redox‐active metalloporphyrin,improves islet function and engraftment in a murine transplant model

Islet transplantation has become a well‐established therapy for select patients with type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluated whether the administration of BMX‐001 (MnTnBuOE‐2‐PyP⁵⁺ [Mn(III) meso‐tetrakis‐(N‐ b ‐butoxyethylpyridinium‐2‐yl)porphyrin]) and its earlier derivative, BMX‐010 (MnTE‐2‐PyP [Mn(III) meso‐tetrakis‐(N‐methylpyridinium‐2‐yl)porphyrin]) could improve islet function and engraftment outcomes. Long‐term culture of human islets with BMX‐001, but not BMX‐010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34 μmol/L BMX‐001 exhibited improved insulin secretion (n = 3 isolations, P < .05) in response to glucose relative to control islets. In addition, 34 μmol/L BMX‐001–supplemented murine islets exhibited significantly reduced apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling, compared with nontreated control islets (P < .05). Murine syngeneic islets transplanted under the kidney capsule at a marginal dose of 150 islets revealed 58% of 34 μmol/L BMX‐001–treated islet recipients became euglycemic (n = 11 of 19) compared with 19% of nontreated control islet recipients (n = 3 of 19, P < .05). Of murine recipients receiving a marginal dose of human islets cultured with 34 μmol/L BMX‐001, 92% (n = 12 of 13) achieved euglycemia compared with 57% of control recipients (n = 8 of 14, P = .11). These results demonstrate that the administration of BMX‐001 enhances in vitro viability and augments murine marginal islet mass engraftment.     

Survival benefit of accepting livers from deceased donors over 70 years old

Livers from older donors (OLDs; age ≥70) are risky and often declined; however, it is likely that some candidates will benefit from OLDs versus waiting for younger ones. To characterize the survival benefit of accepting OLD grafts, we used 2009‐2017 SRTR data to identify 24 431 adult liver transplant (LT) candidates who were offered OLD grafts eventually accepted by someone. Outcomes from the time‐of‐offer were compared between candidates who accepted an OLD graft and matched controls within MELD ± 2 who declined the same offer. Candidates who accepted OLD grafts (n = 1311) were older (60.5 vs. 57.8 years, P < .001), had a higher median MELD score (25 vs. 22, P < .001), and were less likely to have hepatitis C cirrhosis (14.9% vs. 31.2%, P < .001). Five‐year cumulative mortality among those who accepted versus declined the same OLD offer was 23.4% versus 41.2% (P < .001). Candidates who accepted OLDs experienced an almost twofold reduction in mortality (aHR:_0.450.52_0.59, P < .001) compared to those who declined the same offer, especially among the highest MELD (35‐40) candidates (aHR:_0.100.24_0.55, P = .001). Accepting an OLD offer provided substantial long‐term survival benefit compared to waiting for a better organ offer, notably among candidates with MELD 35‐40. Providers should consider these benefits as they evaluate OLD graft offers.     

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.     

Pediatric living donor liver transplantation with large‐for‐size left lateral segment grafts

Usage of “large‐for‐size” left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR‐High = 50) vs GRWR <2.5% (GR‐Low = 27). Median age was higher in the GR‐Low group (40 vs 8 months, P> .0001). Graft (GR‐High: 98%, 98%, 98% vs GR‐Low: 96%, 93%, 93%) and patient (GR‐High: 98%, 98%, 98% vs GR‐Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR‐High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR‐XL = 20) to GRWR <2.5% (GRWR‐Low = 27) revealed that delayed abdominal fascia closure was more common in the GR‐XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large‐for‐size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long‐term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.     

Mitochondrial membrane potential and delayed graft function following kidney transplantation

Delayed graft function (DGF) complicates 20%‐40% of deceased‐donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia‐perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision‐making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single‐center proof‐of‐concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry‐augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964‐28 333 units. Low‐MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = _1.081.38_1.78, P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision‐making through its independent association with DGF.