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.

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.

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.

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.

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.

Metabolic differences between cold stored and machine perfused porcine kidneys: A 1H NMR based study.

Hypothermic machine perfusion (HMP) and static cold storage (SCS) are the two methods used to preserve deceased donor kidneys prior to transplant. This study seeks to characterise the metabolic profile of HMP and SCS porcine kidneys in a cardiac death donor model. Twenty kidneys were cold flushed and stored for two hours following retrieval. Paired kidneys then underwent 24 h of HMP or SCS or served as time zero controls. Metabolite quantification in both storage fluid and kidney tissue was performed using one dimensional 1H NMR spectroscopy. For each metabolite, the net gain for each storage modality was determined by comparing the total amount in each closed system (i.e. total amount in storage fluid and kidney combined) compared with controls. 26 metabolites were included for analysis. Total system metabolite quantities following HMP or SCS were greater for 14 compared with controls (all p < 0.05). In addition to metabolic differences with control kidneys, the net metabolic gain during HMP was greater than SCS for 8 metabolites (all p < 0.05). These included metabolites related to central metabolism (lactate, glutamate, aspartate, fumarate and acetate). The metabolic environments of both perfusion fluid and the kidney tissue are strikingly different between SCS and HMP systems in this animal model. The total amount of central metabolites such as lactate and glutamate observed in the HMP kidney system suggests a greater degree of de novo metabolic activity than in the SCS system. Maintenance of central metabolic pathways may contribute to the clinical benefits of HMP.

Nuclear Magnetic Resonance Strategies for Metabolic Analysis.

NMR spectroscopy is a powerful tool for metabolomic studies, offering highly reproducible and quantitative analyses. This burgeoning field of NMR metabolomics has been greatly aided by the development of modern spectrometers and software, allowing high-throughput analysis with near real-time feedback. Whilst one-dimensional proton (1D-1H) NMR analysis is best described and remains most widely used, a plethora of alternative NMR techniques are now available that offer additional chemical and structural information and resolve many of the limitations of conventional 1D-1H NMR such as spectral overlay. In this book chapter, we review the principal concepts of practical NMR spectroscopy, from common sample preparation protocols to the benefits and theoretical concepts underpinning the commonly used pulse sequences. Finally, as a case study to highlight the utility of NMR as a method for metabolomic investigation, we have detailed how NMR has been used to gain valuable insight into the metabolism occurring in kidneys prior to transplantation and the potential implications of this.

Duplex ultrasound surveillance after carotid artery endarterectomy.

OBJECTIVE: After carotid endarterectomy (CEA), patients have been regularly followed up by duplex ultrasound imaging. However, the evidence for long-term follow-up is not clear, especially if the results from an early duplex scan are normal. This study assessed and systematically reviewed the evidence base for long-term surveillance after CEA and a normal early scan. METHODS: Electronic databases were searched for studies assessing duplex surveillance after CEA in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome for this study was the incidence of restenosis after a normal early scan. The secondary outcome was the number of reinterventions after a normal early scan. RESULTS: The review included seven studies that reported 2317 procedures. Of those patients with a normal early scan, 2.8% (95% confidence interval, 0.7%-6%) developed a restenosis, and 0.4% (95% confidence interval, 0%-0.9%) underwent a reintervention for their restenosis during the follow-up period. CONCLUSIONS: This review confirms that routine postoperative duplex ultrasound surveillance after CEA is not necessary if the early duplex scan is normal.

Risk of post-transplantation diabetes mellitus is greater in South Asian versus Caucasian kidney allograft recipients.

South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians. Case-control matching was therefore undertaken to remove this bias, resulting in 102 recipient pairs. Median follow-up was 50 months (range 4-127 months). Matched groups had similar baseline characteristics, although South Asians compared with Caucasians received more deceased-donor kidneys (74% vs. 43%, respectively, P < 0.001) and were more likely to be CMV positive (77% vs. 43%, respectively, P < 0.001). PTDM incidence was significantly higher in South Asians versus Caucasians (35% vs. 10%, respectively, subhazard ratio 4.2 [95% CI: 2.1-8.5, P < 0.001]). Donor type had significant interaction with ethnicity, with the observed difference in PTDM rates between ethnicities most visible with receipt of deceased-donor kidneys. No significant difference was detected in allograft function, rejection episodes, adverse cardiovascular events or patient/graft survival. South Asians have increased risk of PTDM, especially recipients of deceased kidneys, and recognition of this allows appropriate patient counselling and development of targeted strategies.

Arteriovenous fistula outcomes in the elderly.

OBJECTIVE: Over several decades, there has been an increase in the number of elderly patients requiring hemodialysis. These older patients typically have an increased incidence of comorbidities including diabetes, hypertension, and peripheral vascular disease. We undertook a systematic review of the current literature to assess outcomes of arteriovenous fistula (AVF) formation in the elderly and to compare the results of radiocephalic AVFs vs brachiocephalic AVFs in older patients. METHODS: A literature search was performed using MEDLINE, Embase, PubMed, and the Cochrane Library. All retrieved articles published before December 31, 2014 (and in English) primarily describing the creation of hemodialysis vascular access for elderly patients were considered for inclusion. We report pooled AVF patency rates and a comparison of radiocephalic vs brachiocephalic AVF patency rates using odds ratios (ORs). RESULTS: Of 199 relevant articles reviewed, 15 were deemed eligible for the review. The pooled 12-month primary and secondary AVF patency rates were 53.6% (95% confidence interval [CI], 47.3-59.9) and 71.6% (95% CI, 59.2-82.7), respectively. Comparison of radiocephalic vs brachiocephalic AVF patency rates demonstrated that radiocephalic AVFs have inferior primary (OR, 0.72; 95% CI, 0.55-0.93; P = .01) and secondary (OR, 0.76; 95% CI, 0.58-1.00; P = .05) patency rates. CONCLUSIONS: This meta-analysis confirms that adequate 12-month primary and secondary AVF patency rates can be achieved in elderly patients. Brachiocephalic AVFs have both superior primary and secondary patency rates at 12 months compared with radiocephalic AVFs. These important data can inform clinicians' and patients' decision-making about suitability of attempting AVF formation in older persons.

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.

Hand-assisted laparoscopic donor nephrectomy: are hand port devices really necessary?

BACKGROUND: Hand port devices (HPD) are used routinely for hand-assisted laparoscopic surgery including hand-assisted laparoscopic donor nephrectomy (HALDN). However, the cost of such devices may prove prohibitive, particularly in centers with financial constraints. The authors aimed to identify any adverse effects of performing device-free HALDN. METHODS: A retrospective analysis was performed of patients undergoing HALDN at the authors' unit over a 3-year period (2007-2010). Eighty-four patients underwent device-free HALDN, whereas in 80 patients a HPD was used. The primary endpoint was duration of operation, with secondary endpoints including postoperative wound infections and incisional hernias. RESULTS: here was no difference in duration of operation for the device free (98 minutes; range = 43-215 minutes) compared with the HPD group (94 minutes; range = 36-180 minutes; P = .37). A device was required in 3 (3.6%) patients in which a device-free approach was attempted. There was no difference in either group in terms of rates of postoperative wound infections (0% vs 2.5%, respectively; P = .24) or incisional hernia incidence (1.5% vs 1.4%, respectively; P = .50). CONCLUSION: Device-free HALDN can be performed with no discernable compromise in operating time or patient outcome. This has implications in both cost benefit and translation of this technique to developing units.

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.

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.

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.