Current Evidence and Future Perspectives to Implement Continuous and End-Ischemic Use of Normothermic and Oxygenated Hypothermic Machine Perfusion in Clinical Practice.

The use of high-risk renal grafts for transplantation requires the optimization of pretransplant assessment and preservation reconditioning strategies to decrease the organ discard rate and to improve short- and long-term clinical outcomes. Active oxygenation is increasingly recognized to play a central role in dynamic preservation strategies, independent of preservation temperature, to recondition mitochondria and to restore the cellular energy profile. The oxygen-related decrease in mitochondrial succinate accumulation ameliorates the harmful effects of ischemia-reperfusion injury. The differences between normothermic and hypothermic machine perfusion with regard to organ assessment, preservation, and reconditioning, as well as the logistic and economic implications, are factors to take into consideration for implementation at a local level. Therefore, these different techniques should be considered complementary to the perfusion strategy selected depending on functional intention and resource availability. This review provides an overview of the current clinical evidence of normothermic and oxygenated hypothermic machine perfusion, either as a continuous or end-ischemic preservation strategy, and future perspectives.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Simply Adding Oxygen during Hypothermic Machine Perfusion to Combat the Negative Effects of Ischemia-Reperfusion Injury: Fundamentals and Current Evidence for Kidneys.

The use of high-risk renal grafts for transplantation requires optimization of pretransplant preservation and assessment strategies to improve clinical outcomes as well as to decrease organ discard rate. With oxygenation proposed as a resuscitative measure during hypothermic machine preservation, this review provides a critical overview of the fundamentals of active oxygenation during hypothermic machine perfusion, as well as the current preclinical and clinical evidence and suggests different strategies for clinical implementation.

Macroscopic assessment of the quality of cold perfusion after deceased-donor kidney procurement: A United Kingdom population-based cohort study.

Concern regarding the quality of cold perfusion (QOP) during macroscopic assessment of procured kidneys is a common reason for discard. In the UK, QOP is routinely graded by both retrieving and implanting teams during back-bench surgery as: 1 (good), 2 (fair), 3 (poor) or 4 (patchy). We evaluated the association of this grading with organ utilization, graft outcomes, and agreement between teams. Data on all deceased-donor kidneys procured between January 2000 and December 2016 were analyzed for discard rates, while association with graft outcomes was studied in single adult transplants. Of 31,167 kidneys procured, 90.6%, 5.7%, 1.7%, and 2.1% were assigned grades 1, 2, 3, and 4, respectively, at retrieval. QOP was an independent risk factor of discard, with the highest rates observed in grade 3 kidneys (41.8%), compared to 6.5% in grade 1 (aOR 7.67, 95% CI 5.44-10.82, p < .001). Grading at retrieval was an independent predictor of delayed graft function (p = .019) and primary non-function (p = .001), but not long-term graft survival (p = .111). Implanting grade was an independent predictor of all three outcomes (p < .001, p < .001, and p = .002, respectively). Consistency of grading between teams was poor (Kappa = 0.179). QOP influences utilization and predicts outcomes, but a standardized and validated scoring system is required.

Recipient Sex Differences in Kidney Graft Survival Are Influenced by Donor Sex and Recipient Age.

OBJECTIVES: An age-dependent interaction has been described for the effect of donor-recipient sex mismatch on outcomes after kidney transplant in the United States. However, this has not been verified or tested in a different cohort from another country. MATERIALS AND METHODS: Data of 25 140 deceased donor kidney transplant recipients (2000-2016) were retro-spectively analyzed at a population-cohort level using the United Kingdom transplant registry. Within sub-groups of donor sex, associations between recipient sex and death-censored graft survival were assessed for the cohort as a whole and within recipient age subgroups. RESULTS: No differences in graft survival were detected between female versus male recipients of male donor kidneys (adjusted hazard ratio: 1.05; P = .227). However, a significant interaction between the age and sex of recipients was identified (P = .007). Female recipients aged 25 to 44 years had significantly shorter graft survival than male recipients (adjusted hazard ratio: 1.27; P = .003), but this effect was reversed in recipients who were 45 years or older (adjusted hazard ratio: 0.94; P = .258), where there was a nonsignificant tendency for longer graft survival in females. No such effect was observed in the subgroup of female donor transplants, with no significant difference between female versus male recipients overall (adjusted hazard ratio: 1.02; P = .638) and no significant interaction with age (P = .470). CONCLUSIONS: Graft survival is influenced by the combination of recipient age and sex in recipients of male donor kidneys only. This work demonstrates findings broadly similar to published reports but presents differences in observed effect sizes among certain subgroups. Our research suggests further work is warranted to explore personalized approaches to age- and sex-adapted immunosuppression.

Kidney transplantation outcomes for adult recipients of pediatric donor kidneys.

Despite a paucity of data assessing transplantation of deceased-donor pediatric donor kidneys into adult recipients, utilization of pediatric organs is declining in the UK, likely due to concerns that such organs may have inferior outcomes. However, we hypothesized that these concerns may be unfounded. As such, the aim of the study was to compare kidney transplant outcomes between adult recipients of pediatric and adult deceased-donor organs. Data were collected from the UK Transplant Registry for all adult (18+ years) deceased-donor single-kidney transplant recipients between January 2000 and January 2016. Univariable and multivariable analyses were undertaken, to compare a range of outcomes between recipients of kidneys from pediatric and adult donors. Transplants were stratified by the donor age (years) as follows: 0-16 (n = 666), 17-18 (n = 465), and 19-44 (n = 7378). Recipients of pediatric donor kidneys were observed to have improved long-term graft function, with a median creatinine at 1 year of 109 vs. 117 µmol/L for recipients of donors aged 0-16 vs. 19-44 years (P < .001). However, on multivariable analysis, this was not found to correspond to a significant difference in patient (P = .914) or graft survival (P = .190) between the donor age groups. Subgroup analysis within the younger donors found no significant differences in recipient outcomes between donors aged 0-6, 7-12, and 13-16 years. In this population cohort study, we identified excellent outcomes among adult recipients of pediatric donor kidneys. Pediatric donors are a valuable source of organs for adult recipients in an era where organ demand is rising.

Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model.

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O2 uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.

Donor-recipient Sex Differences Do Not Affect Survival Outcomes After Kidney Transplantation: A Population Cohort Study.

BACKGROUND: Donor factors can influence decision making for organ utilization for potential kidney transplant candidates. Prior studies exploring the effect of donor-recipient sex matching on kidney transplant outcomes have reported heterogenous and conflicting results. The aim of this contemporary population-cohort analysis was to explore the effect of donor-recipient sex matching on kidney transplant outcomes in the United Kingdom. METHODS: In this retrospective, observational study, we analyzed all patients receiving kidney-alone transplants between 2003 and 2018 using UK Transplant Registry data. Stratified by recipient sex, outcomes were compared between male and female donors with univariable/multivariable analyses. RESULTS: Data were analyzed for 25 140 recipients. Of these, 13 414 (53.4%) of kidneys were from male donors and 15 690 (62.4%) of recipients were male. The odds of initial graft dysfunction (delayed graft function/primary nonfunction) were significantly lower for female donor kidneys transplanted into both male (adjusted odds ratio = 0.89, 95% confidence interval [CI] = 0.80-0.98, P = 0.019) and female (adjusted odds ratio = 0.81, 95% CI = 0.71-0.93, P = 0.003) recipients. Male recipients of female donor kidneys had creatinine levels at 1 year that were 6.3% higher (95% CI = 4.8%-7.7%, P < 0.001) than male recipients of male donor kidneys, with a similar sex difference of 4.1% (95% CI = 2.1%-6.1%, P < 0.001) observed within female recipients. However, neither patient nor graft survival was found to differ significantly by donor sex on either univariable or multivariable analysis. CONCLUSIONS: Our data provide contemporary data on sex mismatch for recipient counseling and reassurance with regards to equivalent long-term clinical outcomes based upon donor sex.

Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model.

BACKGROUND: The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model. METHODS: The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation. Kidneys stored in 22-hour standard HMP (n = 6) and 22-hour static cold storage (n = 6) conditions served as controls. The follow-up after autotransplantation was 13 days. RESULTS: High PO2 resulted in a 3- and 10-fold increase in perfusate PO2 compared with low HMPO2 and standard HMP, respectively. Both HMPO2 groups were associated with superior graft recovery compared with the control groups. Oxygenation was associated with a more rapid and sustained decrease in renal resistance. While there was no difference in functional outcomes between both HMPO2 groups, there were clear metabolic differences with an inverse correlation between oxygen provision and the concentration of major central metabolites in the perfusion fluid but no differences were observed by oxidative stress and metabolic evaluation on preimplantation biopsies. CONCLUSIONS: While this animal study does not demonstrate any advantages for early graft function for high perfusate PO2, compared with low perfusate PO2, perfusate metabolic profile analysis suggests that aerobic mechanism is better supported under high perfusate PO2 conditions.

Hypoalbuminaemia at time of surgery is associated with an increased risk for overall graft loss after kidney transplantation.

AIM: The aim of this retrospective cohort study was to investigate whether pre-operative hypoalbuminaemia (<35 g/L) is associated with adverse outcomes post-kidney transplantation. METHODS: Our retrospective, single-centre analysis included all patients who received their kidney transplant between 2007 and 2017, with documented admission albumin levels prior to surgery. Survival analyses were undertaken to explore the relationship of pre-transplant hypoalbuminaemia versus other baseline variables upon post-transplant outcomes. RESULTS: We analysed 1131 kidney allograft recipients transplanted at our centre (2007-2017), with median follow-up 746 days (interquartile range 133-1750 days). Kidney transplant recipients with pre-operative hypoalbuminaemia were more likely older, female, recipients of deceased-donor kidneys and to have longer cold ischaemic times. Recipients with pre-operative hypoalbuminaemia had longer hospital admissions post-operatively but no difference in delayed graft function rates. There was no difference in 1 year creatinine but recipients with hypoalbuminaemia had reduced risk for cellular rejection. We observed significantly worse patient survival (83.2% vs 90.7%, P < 0.001) and overall graft survival (72.5% vs 82.0%, P < 0.001) for recipients with hypoalbuminaemia vs normal albumin levels, respectively, but no difference in death-censored graft survival. In a Cox regression model, adjusted for baseline pre-operative variables, hypoalbuminaemia was independently associated with an increased risk for overall graft loss after kidney transplantation (hazard ratio 1.468, 95% confidence interval 1.087-1.982, P = 0.012). CONCLUSION: Pre-operative hypoalbuminaemia is an independent risk factor for overall graft loss after kidney transplantation. Further work is warranted to investigate the underlying pathophysiology to determine what supportive measures can be undertaken to attenuate adverse post-transplant outcomes.

Deceased-Donor Smoking History Is Associated With Increased Recipient Mortality After Kidney Transplant: A Population-Cohort Study.

OBJECTIVES: Historical data have suggested that donor smoking is associated with detrimental clinical outcomes for recipients of kidneys from deceased donors. However, the effects of smoking status of a kidney donor on the outcomes of the recipient in a contemporary setting of immunosuppression and transplant practice have not yet been ascertained. MATERIALS AND METHODS: This retrospective, population-cohort study analyzed data of all deceased-donor kidney-alone transplant procedures performed in the United Kingdom between April 2001 and April 2013. Our study included 11?199 deceased-donor kidney allograft recipients, with median follow-up of 46 months posttransplant. RESULTS: In our cohort, 5280 deceased donors (47.1%) had a documented history of smoking. Deceased donors with versus those without smoking history were more likely to be younger (mean age of 48 vs 50 years; P < .001), be of white ethnicity (96.6% vs 95.3%; P < .001), and have brain death before donation (77.1% vs 74.9%; P = .006). On unadjusted survival analyses, overall patient survival was significantly shorter in patients who received kidney allografts from deceased donors with smoking history (hazard ratio of 1.12, 95% confidence interval, 1.00-1.25; P = .044). No significant association was seen for death-censored or overall graft survival. Our multivariate survival analyses showed that, after accounting for confounding factors, the effects of donor smoking status remained significant for patient survival (hazard ratio of 1.16, 95% CI, 1.03-1.29; P =.011) but not graft survival. CONCLUSIONS: This population-cohort study suggests that deceased-donor kidneys from smokers contribute to an increased risk of death for kidney allograft recipients. These study findings imply donor smoking history should be factored into the risk stratification decision for recipient selection to optimize decision making; however, further clarification and validation of these data are warranted.

The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion.

BACKGROUND: Supplemental oxygenation of the standard hypothermic machine perfusion (HMP) circuit has the potential to invoke favorable changes in metabolism, optimizing cadaveric organs before transplantation. METHODS: Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired donation after circulatory death model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labeled glucose.Perfusate, end-point renal cortex, and medulla samples underwent metabolomic analysis using 1-dimension and 2-dimension nuclear magnetic resonance experiments in addition to gas chromatography-mass spectrometry. Analysis of C-labeled metabolic products was combined with adenosine nucleotide levels and differences in tissue architecture. RESULTS: Metabolomic analysis revealed significantly higher concentrations of universally labeled lactate in the cortex of HMP/Air versus HMP/O2 kidneys (0.056 mM vs 0.026 mM, P < 0.05). Conversely, newly synthesized [4,5-C] glutamate concentrations were higher in the cortex of HMP/O2 kidneys inferring relative increases in tricarboxylic acid cycle activity versus HMP/Air kidneys (0.013 mmol/L vs 0.003 mmol/L, P < 0.05). This was associated with greater amounts of adenoside triphosphate in the cortex HMP/O2 versus HMP/Air kidneys (19.8 mmol/mg protein vs 2.8 mmol/mg protein, P < 0.05). Improved flow dynamics and favorable ultrastructural features were also observed in HMP/O2 kidneys. There were no differences in thiobarbituric acid reactive substances and reduced glutathione levels, tissue markers of oxidative stress, between groups. CONCLUSIONS: The supplementation of perfusion fluid with high-concentration oxygen (95%) results in a greater degree of aerobic metabolism versus aeration (21%) in the nonphysiological environment of HMP, with reciprocal changes in adenoside triphosphate levels.

The Influence of Donor to Recipient Size Matching on Kidney Transplant Outcomes.

BACKGROUND: Nephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios. METHODS: Data for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry. We used weight as a surrogate marker for kidney size and defined the following mismatch categories (donor weight/recipient weight × 100): less than 75% (small donor kidney), 75% to 125% (weight matched kidney), and greater than 125% (large donor kidney). Univariable and multivariable analyses were undertaken to assess the relationship between this marker and patient outcomes. RESULTS: Outcomes for 11 720 transplants were analyzed with weight mismatch stratified as follows; small donor kidney (n = 1608, 13.7%), weight matched kidney (n = 7247, 61.8%) and large donor kidney (n = 2865, 24.4%). On multivariable analysis, no significant differences were detected in overall (P = 0.876) or death-censored (P = 0.173) graft survival, or in rates of delayed graft function (P = 0.396) between these 3 groups. However, 12-month creatinine levels were found to decline progressively across the groups (P < 0.001), with adjusted averages of 144.2 µmol/L for recipients of small donor kidneys, 134.7 µmol/L in weight matched kidneys, and 124.9 µmol/L in recipients of large donor kidneys. In addition, patient survival was found to be significantly shorter in recipients of larger kidneys than those with weight matched kidneys (hazard ratio, 1.21; 95% confidence interval, 1.05-1.40; P = 0.009), which is inconsistent with the existing literature. CONCLUSIONS: Our data demonstrate that 12-month creatinine is influenced by donor-to-recipient difference in body weight, but that no such difference is observed for either delayed graft function or death-censored graft survival. However, we observed increased mortality in recipients receiving larger kidneys; an observation which conflicts with the existing literature and warrants further investigation.

Recipient Outcomes From Nondirected Live Kidney Donors: A UK-based Cohort Study.

BACKGROUND: Increasing numbers of patients with end-stage renal failure are receiving kidneys from nondirected kidney donors (NKDs), also known as altruistic donors. Transplant outcomes for recipients of such kidneys are largely inferred from studies on specified kidney donors (SKDs), which may be inaccurate due to differences in donor, recipient and transplant specific factors. We report the outcomes for recipients of NKD in the United Kingdom. METHODS: Outcomes for 6861 patients receiving a living donor kidney transplant between January 2007 and December 2014 were analyzed using both the National Health Service Blood and Transplant and the UK Renal Registry datasets. Graft and patient outcomes were compared for patients receiving NKD and SKD organs using univariable and multivariable analyses. RESULTS: There was significant discordance between the NKD and SKD donors and recipients. These included increased donor age (median, 58 years vs 47 years; P < 0.001) and higher rates of hemodialysis and previous transplants in the NKD group (both P < 0.001). Despite such markers of increased risk among both donors and recipients of NKD kidneys, there was no difference in graft survival on univariable (hazard ratio, 1.20; 95% confidence interval, 0.77-1.86; P = 0.419) or multivariable analysis (hazard ratio, 1.13; 95% confidence interval, 0.65-1.95; P = 0.665). CONCLUSIONS: Despite some markers of transplant complexity, nondirected kidney donor organs are an excellent source of organs for transplantation.

Repatriation of Patients to Referral Centers and Outcomes After Kidney Transplantation: A Single-center Analysis From the United Kingdom.

BACKGROUND: The aim of this study was to compare posttransplant outcomes of kidney allograft recipients between those followed up at transplant centers and those that were repatriated back to referral renal units. METHODS: We analyzed data for 1375 consecutive patients transplanted in a single center in the United Kingdom. Patients were stratified into 3 groups: (1) externally referred patients with repatriation back for external follow-up (repatriated, n = 463), (2) externally referred patients not repatriated and followed-up internally at transplant center (nonrepatriated, n = 365), and (3) internally referred patients within transplant center with continued internal transplant center follow-up (internal, n = 547). Patient and death-censored graft survival were compared between groups on both univariable and multivariable analyses. RESULTS: Baseline comparisons found that the nonrepatriated group had increased risk for prolonged length of stay and delayed graft function compared with repatriated patients. The nonrepatriated group had significantly shorter survival compared to the repatriated patients (90.2% vs 94.1% at 5 years, P = 0.013), which persisted after adjustment for confounders on multivariable analysis (hazard ratio, 1.86; 95% confidence interval, 1.06-3.28; P = 0.032). Death-censored graft survival was not found to differ significantly between the 3 groups (P = 0.192). CONCLUSIONS: Our results provide reassurance regarding repatriation of care after kidney transplantation for the United Kingdom. Nonrepatriated patients are identified as a high-risk group for increased mortality, but further investigation is warranted to probe this heterogeneous group and validate in a non-United Kingdom cohort.

Black Ethnicity is Not a Risk Factor for Mortality or Graft Loss After Kidney Transplant in the United Kingdom.

OBJECTIVES: There are conflicting reports in the literature regarding outcomes after kidney transplant for patients of black ethnicity. To investigate further, we compared outcomes for black versus white kidney transplant recipients in a single UK transplant center. MATERIALS AND METHODS: We analyzed 1066 kidney transplant recipients (80 black patients, 986 white patients) within a single-center cohort (2007-2017) in the United Kingdom, with cumulative 4446 patient-year follow-up. Data were electronically extracted from the Department of Health Informatics database for every study recruit, with manual data linkage to the UK Transplant Registry (for graft survival, delayed graft function, and rejection data) and Office for National Statistics (for mortality data). Primary outcomes of interest were graft/patient survival. RESULTS: Black recipients have increased baseline risk profiles with longer wait times, difficulty in matching, worse HLA matching, more socioeconomic deprivation, and lower rates of living kidney donors. Postoperatively, black versus white recipients had increased risk for delayed graft function (34.3% vs 10.2%; P < .001), increased 1-year rejection (16.7% vs 7.3%; P = .012), higher 1-year creatinine levels (166 vs 138 mmol/L; P = .003), and longer posttransplant length of stay (14.5 vs 9.5 days; P = .020). Although black recipients did not have increased risk of death versus white recipients (10.0% vs 11.0%, respectively; P = .486), they did have increased risk for death-censored graft loss (23.8% vs 11.1%; P = .002). However, in an adjusted Cox regression model, black ethnicity was not associated with increased risk for death-censored graft loss (hazard ratio of 1.209, 95% confidence interval, 0.660-2.216; P = .539). CONCLUSIONS: Black kidney transplant recipients in the United Kingdom have increased risk of adverse graft-related outcomes due to high-risk baseline variables rather than their black ethnicity per se.

The impact of donor body mass index on outcomes after deceased kidney transplantation - a national population-cohort study.

The aim of this study was to determine the effect of donor body mass index (BMI) on deceased donor kidney transplant outcomes. Data were collected from the UK Transplant Registry for all deceased donor kidney transplant recipients between January 2003 and January 2015. Univariable and multivariable analyses were undertaken to assess the impact of donor BMI on a range of outcomes. Donor BMI (kg/m2 ) was stratified as <18.5 (n = 380), 18.5-25.0 (n = 6890), 25.1-30.0 (n = 6669), 30.1-35.0 (n = 2503) and >35.0 (n = 1148). The prevalence of delayed graft function increased significantly with donor BMI (P < 0.001), with an adjusted odds ratio of 1.38 (95% CI: 1.16-1.63) for the >35.0 vs. 18.5-25.0 groups. However, there was no significant association between donor BMI and 12-month creatinine (P = 0.550), or patient (P = 0.109) or graft (P = 0.590) survival. In overweight patients, increasing donor BMI was associated with a significant increase in warm ischaemia time and functional warm ischaemia time, by an average of 4.6% (P = 0.043) and 5.2% (P = 0.013) per 10.0 kg/m2 . However, rising warm ischaemic time and functional warm ischaemic time was not significantly associated with delayed graft function, 12-month creatinine levels, graft loss or patient death. In this population cohort study, we identified no significant association between donor BMI and long-term clinical outcomes in deceased donor kidney transplantation.

Ethnicity matching and outcomes after kidney transplantation in the United Kingdom.

BACKGROUND: Kidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes. METHODS: We undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003-2015, with data censored at 1st October 2016. We included 27,970 recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR 716-2,869 days). Unadjusted and adjusted Cox regression survival analyses were performed to investigate ethnicity effect on risk for graft loss and mortality. RESULTS: In unadjusted analyses, matched ethnicity between donors-recipients resulted in better outcomes for delayed graft function, one-year creatinine, graft and patient survival but these differed by ethnicity matches. Compared to white-to-white transplants, risk for death-censored graft loss was higher in black-to-black and similar among Asian-to-Asian transplants, but mortality risk was lower for both black-to-black and Asian-to-Asian transplants. In Cox regression models, compared to white donors, we observed higher risk for graft loss with both south Asian (HR 1.38, 95%CI 1.12-1.70, p = 0.003) and black (HR 1.66, 95%CI 1.30-2.11, p<0.001) donated kidneys independent of recipient ethnicity. We observed no mortality difference with south Asian donated kidneys but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21-2.35, p = 0.002). Matching ethnicities made no significant difference in any Cox regression model. Similar results were observed after stratifying our analysis by living and deceased-donor kidney transplantation. CONCLUSIONS: Our data confirm inferior outcomes associated with non-white kidney donors for kidney transplant recipients of any ethnicity in a risk-adjusted model for the United Kingdom population. However, contrary to non-renal transplant literature, we did not identify any survival benefits associated with donor-recipient ethnicity matching.

Mortality risk after cancer diagnosis in kidney transplant recipients: the limitations of analyzing hospital administration data alone.

Administrative data are frequently used for epidemiological studies but its usefulness to analyze cancer epidemiology after kidney transplantation is unclear. In this retrospective population-based cohort study, we identified every adult kidney-alone transplant performed in England (2003-2014) using administrative data from Hospital Episode Statistics. Results were compared to the hospitalized adult general population in England to calculate standardized incidence and mortality ratios. Data were analyzed for 19,883 kidney allograft recipients, with median follow-up 6.0 years' post-transplantation. Cancer incidence was more common after kidney transplantation compared to the general population in line with published literature (standardized incidence ratio 2.47, 95% CI: 2.34-2.61). In a Cox proportional hazards model, cancer development was associated with increasing age, recipients of deceased kidneys, frequent readmissions within 12 months post-transplant and first kidney recipients. All-cause mortality risk for kidney allograft recipients with new-onset cancer was significantly higher compared to those remaining cancer-free (42.0% vs. 10.3%, respectively). However, when comparing mortality risk for kidney allograft recipients to the general population after development of cancer, risk was lower for both cancer-related (standardized mortality ratio 0.75, 95% CI: 0.71-0.79) and noncancer-related mortality (standardized mortality ratio 0.90, 95% CI: 0.85-0.95), which contradicts reported literature. Although some plausible explanations are conceivable, our analysis likely reflects the limitations of administrative data for analyzing cancer data. Future studies require record linkage with dedicated cancer registries to acquire more robust and accurate data relating to cancer epidemiology after transplantation.