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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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m 2 ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant., (© 2019 Steunstichting ESOT.)

Objective: Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored., Design and Methods: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs., Main Outcome Measures: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected., Results: Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01)., Conclusions: Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Physical fatigue is debilitating and common among kidney transplant recipients (KTRs). This study investigated the mechanistic aetiology of physical fatigue in this setting through examinations of muscle mass, muscular and cardiovascular function, and perceived exertion. The incidence of physical fatigue, its association with quality of life (QoL), and the predictors of perceived exertion, were evaluated. This single-centre observational cross-sectional study enrolled 55 KTRs. Muscle mass was quantified using dual-energy x-ray absorptiometry. Muscular function was assessed by jumping mechanography. Cardiovascular function (maximal oxygen consumption and oxygen pulse) was estimated during submaximal exercise testing, with perceived exertion determined using age-adjusted Borg scale-ratings. Physical fatigue was measured using Multi-Dimensional Fatigue Inventory-20. QoL was assessed using Medical Outcomes Study Short Form-36. Demographic, clinical, nutritional, psychosocial and behavioural predictors of perceived exertion were assessed. Of clinical importance, increased perceived exertion was the only independent predictor of physical fatigue (P = 0.001), with no association found between physical fatigue and muscular or cardiovascular parameters. Physical fatigue occurred in 22% of KTRs, and negatively impacted on QoL (P < 0.001). Predictors of heightened perception included anxiety (P < 0.05) and mental fatigue (P < 0.05). Perception is a key determinant of physical fatigue in KTRs, paving the way for future interventions., (© 2015 Steunstichting ESOT.)

Background: Laparoscopic living-donor nephrectomy (LDN) exerts systemic effects causing transaminitis and increased urinary neutrophil gelatinase-associated lipocalm (NGAL) excretion. Hand-assisted laparoscopic donor nephrectomy, which tends to be shorter with less pneumoperitoneum, may be hypothesized to produce less systemic stimulation than total laparoscopic LDN., Methods: Serial urine and serum samples were collected from 15 patients undergoing HALDN. Samples were analyzed for NGAL and kidney injury molecule 1 (KIM-1) levels preoperatively and 24 hours post-surgery. Data relating to alanine aminotransferase, creatinine, and estimated glomerular filtration rate was also analyzed in 48 live donors preoperatively and at 24 hours and 48 hours post-surgery and compared to published data on LDN., Results: Expected changes to creatinine and estimated glomerular filtration rates were observed in the donors. Compared to the preoperative levels, alanine aminotransferase levels showed a significant decrease at 24 hours (P = .004) and were not significantly different from baseline levels at 48 hours (P = .08). Serum KIM-1 and NGAL levels remained unchanged (P = .89 and P = .14, respectively) at 24 hours after donation. Similarly, urinary levels of KIM-1 and NGAL were not statistically significantly different after donation. Mean operating time for this cohort was 1 hour, 36 minutes., Conclusions: In contrast to other published data, our cohort did not exhibit changes to liver function tests or biomarker changes after donor nephrectomy. This could be because of the lower operative time (96 minutes vs. 216 minutes) or because of the intermittent release of the pneumoperitoneum in the hand-assisted method which may exert less of a systemic inflammatory response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time., Materials and Methods: Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list., Results: There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications., Conclusions: This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

Background: Deceased kidney donors are increasingly "marginal," and many have risk factors for acute kidney injury (AKI) that may impact on subsequent renal transplant outcome. Despite this, determining the presence of AKI at the time of deceased organ donation remains difficult., Methods: Urine samples from 182 brainstem dead multi-organ donors (all of whom donated hearts that were transplanted) were analyzed for a Luminex(™) panel of biomarkers linked with AKI. This included KIM-1, NGAL, IFN-γ, TNF-α, cystatin C, Fractalkine and vascular endothelial growth factor. Levels were correlated to early renal transplant outcomes, most specifically delayed graft function., Results: Donor urinary KIM-1 levels were significantly higher in donors whose kidneys displayed aberrant early function (p = 0.011). Fractalkine levels showed a trend toward elevation in such donors but uncorrected this did not attain significance. No correlation occurred with the remaining biomarkers., Conclusions: KIM-1 appears to show promise as a marker for AKI in deceased cardiac organ donors. The availability of a lateral flow device (Renastick(™) ) for KIM-1 that also demonstrates higher urinary KIM-1 levels in donors whose kidneys show aberrant initial function (p = 0.03), makes KIM-1 a potential indicator of AKI that may merit further evaluation for its application at the donor bedside., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Non-Herlitz junctional epidermolysis bullosa (NH-JEB) is a very rare inherited disorder, with an array of complications. We present the case of a 33-year-old patient of Chinese origin, diagnosed with NH-JEB in childhood, who developed severe IgA nephropathy. His renal impairment was initially treated by haemodialysis. He underwent successful renal transplantation, resulting in normalization of his renal function. To our knowledge, this is the first report of renal transplantation in a patient with epidermolysis bullosa, which should support use of this intervention in other similar cases., (© 2014 British Association of Dermatologists.)

Acute rejection is a significant problem for patients undergoing HLA-incompatible renal transplantation, affecting between 12 and 53% of patients. Any mechanism of detecting rejection in advance of current methods would offer significant benefit. This study aimed to evaluate whether serum biomarkers could predict rejection in HLAi transplants recipients. Sera from 94 HLAi transplant recipients from a single centre were analysed for a panel of biomarkers including: NGAL, KIM-1, IP-10, cystatin C, cathepsin L and VEGF. Biomarker levels pre-operatively, day 1 and at day 30 post-transplant were correlated with the development of early rejection. Significantly higher levels of IP-10 and NGAL were seen on day 1 following transplant in those patients who developed acute rejection (P < 0.001 and 0.005) and generated AUC of 0.73 and 0.67, respectively. No differences were seen for the other biomarkers or at the other time points. In this study cohort, IP-10 and NGAL have demonstrated good predictive ability for the development of acute rejection at a very early time point. They may have a role in identifying patients at higher risk for rejection and stratifying immunosuppression or surveillance., (© 2014 Steunstichting ESOT.)

Background: Fatigue has been underinvestigated in stable kidney transplant recipients (KTRs). The objectives of this study were to investigate the nature, severity, prevalence, and clinical awareness of fatigue in medically stable KTRs, examine the impact of fatigue on quality of life (QoL), and explore the underlying causes of posttransplantation fatigue., Methods: This single-center cross-sectional study enrolled 106 stable KTRs. Multi-dimensional Fatigue Inventory-20 was used to measure five fatigue dimensions: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue. Clinical awareness of fatigue was determined by reviewing medical records. QoL was assessed by Medical Outcomes Study Short Form-36 Questionnaire. Demographic, clinical, psychosocial, and behavioral parameters were evaluated as fatigue predictors., Results: Fatigue was found in 59% of KTRs. Only 13% had this symptom documented in medical records. Fatigue in KTRs was in the same range as chronically unwell patients, with Physical Fatigue, Reduced Activity, and Reduced Motivation approached levels observed in chronic fatigue syndrome. All fatigue dimensions significantly and inversely correlated with QoL (P<0.001 for all associations). Demographic predictors were male, older age, and non-Caucasian ethnicity (P≤0.05 for all associations). Clinical predictors included elevated highly sensitive C-reactive protein (inflammation), decreased estimated glomerular filtration rate (graft dysfunction), and reduced lean tissue index (P≤0.05 for all associations). Psychosocial and behavioral predictors were inferior sleep quality, anxiety, and depression (P<0.01 for all associations)., Conclusions: Fatigue is common and pervasive in clinically stable KTRs. It is strongly associated with reduced QoL. This study identified modifiable fatigue predictors and sets the scene for future interventional studies.

Background: Guidelines suggest tuberculosis (TB) prophylaxis in renal transplant recipients originating in endemic areas or in those at risk from non-endemic countries. Concern remains that these guidelines may fail to provide adequate prophylaxis for a cohort of patients who remain at potential risk. We aimed to determine variation patterns among different transplant units within the United Kingdom (UK) with regard to TB prophylaxis policy., Methods: The renal pharmacist at each of the 25 UK renal transplant centers was contacted. Specific information was obtained relating to drug prophylaxis given, duration of treatment, as well as which transplant recipients were eligible for treatment., Results: A 96% response rate (24/25 centers) was achieved. Prophylaxis regimens varied from no prophylaxis to isoniazid 300 mg given life-long. The most common duration of treatment was 6 months post transplantation (at 7 centers). Variations existed in the concurrent use of pyridoxine. A wide discrepancy was seen in the determination of who should receive prophylaxis, with no clear association with frequency of TB incidence in the region., Conclusions: A marked discrepancy exists among national renal transplant units in pharmacologic prophylaxis for TB, as well in the selection of individuals for this treatment., (© 2012 John Wiley & Sons A/S.)

Background: Although risk factors for kidney transplant failure are well described, prognostic risk scores to estimate risk in prevalent transplant recipients are limited., Study Design: Development and validation of risk-prediction instruments., Setting & Participants: The development data set included 2,763 prevalent patients more than 12 months posttransplant enrolled into the LOTESS (Long Term Efficacy and Safety Surveillance) Study. The validation data set included 731 patients who underwent transplant at a single UK center., Predictor: Estimated glomerular filtration rate (eGFR) and other risk factors were evaluated using Cox regression., Outcome: Scores for death-censored and overall transplant failure were based on the summed hazard ratios for baseline predictor variables. Predictive performance was assessed using calibration (Hosmer-Lemeshow statistic), discrimination (C statistic), and clinical reclassification (net reclassification improvement) compared with eGFR alone., Results: In the development data set, 196 patients died and another 225 experienced transplant failure. eGFR, recipient age, race, serum urea and albumin levels, declining eGFR, and prior acute rejection predicted death-censored transplant failure. eGFR, recipient age, sex, serum urea and albumin levels, and declining eGFR predicted overall transplant failure. In the validation data set, 44 patients died and another 101 experienced transplant failure. The weighted scores comprising these variables showed adequate discrimination and calibration for death-censored (C statistic, 0.83; 95% CI, 0.75-0.91; Hosmer-Lemeshow χ(2)P = 0.8) and overall (C statistic, 0.70; 95% CI, 0.64-0.77; Hosmer-Lemeshow χ(2)P = 0.5) transplant failure. However, the scores failed to reclassify risk compared with eGFR alone (net reclassification improvements of 7.6% [95% CI, -0.2 to 13.4; P = 0.09] and 4.3% [95% CI, -2.7 to 11.8; P = 0.3] for death-censored and overall transplant failure, respectively)., Limitations: Retrospective analysis of predominantly cyclosporine-treated patients; limited study size and categorization of variables may limit power to detect effect., Conclusions: Although the scores performed well regarding discrimination and calibration, clinically relevant risk reclassification over eGFR alone was not evident, emphasizing the stringent requirements for such scores. Further studies are required to develop and refine this process., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite comorbidity associated with chronic kidney disease, little data exist applying comorbidity scoring systems to renal transplant recipients. This study compared the performance of 7 established comorbidity scores in predicting mortality after kidney transplantation., Materials and Methods: We retrospectively analyzed prospectively collected data from 2033 incident renal transplant recipients. Comorbidity was assessed at baseline, and the following scores were derived: Recipient Risk Score, Charlson Comorbidity Index, Age-adjusted Charlson Comorbidity Index, Modified End-Stage Renal Disease Charlson Comorbidity Index, Foley Score, Wright-Khan Index, and Davies Index. Cox models investigated the association of each comorbidity score with mortality; performance characteristics were tested using receiver operating characteristic curve analysis., Results: Age-stratified Cox analyses showed the Recipient Risk Score-based model displayed the best fit, and receiver operating characteristic curve analysis showed the Recipient Risk Score demonstrated greatest predictive use (5-year mortality c-statistic: 0.787). The independent effect of age on mortality was demonstrated after analysis of scores not containing age as a component (the Charlson Comorbidity Index, the Modified End-Stage Renal Disease Charlson Comorbidity Index, the Davies Index); addition of age to these scores improved fit., Conclusions: Of the currently available comorbidity scores, the Recipient Risk Score demonstrated greatest use. This has implications for deceased-donor allocation algorithms, assessment of confounders in clinical research, and potentially, individual patient management.

Objectives: In animal models of transplantation, chemokine receptors have been shown to direct the infiltration of T cells in immune responses and inflammation and to be critical in cellular recruitment. Although the chemokine receptors CXCR3 and CCR5 and their ligands have been found during acute rejection in transplanted human kidneys, the kinetics of expression on peripheral blood lymphocytes is unknown., Materials and Methods: Using a whole-blood red-cell lysis fluorescence-activated cell sorter, serial expressions of CXCR3 and CCR5 on T-cell subsets were analyzed in 19 human renal transplant recipients following transplant., Results: In patients developing allograft rejection (n=6), increased expression of CXCR3 occurred on the surface of CD4+ T cells by the third day after transplant. In patients remaining rejection free (n=13), decreased expression was seen. In patients experiencing allograft rejection and in those remaining rejection free, levels of CXCR3 on CD8+ T cells and CCR5 on CD4+ and CD8+ cells remained stable throughout the study., Conclusions: During allograft rejection, expression of CXCR3, but not CCR5, increases on peripheral CD4+ T cells prior to clinical evidence of allograft rejection and remains elevated for more than 2 weeks following transplantation. This may represent a specific molecular target for identifying and preventing allograft rejection.