2026
Multicentre Collaborative Prospective Cohort Study Investigating the Impact of Enhanced Recovery After Surgery on Kidney Transplant Outcomes: The CRAFT Study
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Abstract
Perioperative complications are common in kidney transplantation. Enhanced recovery after surgery (ERAS) is a well-established multimodal perioperative care pathway designed to improve patient outcomes, however, its efficacy in renal transplant remains poorly described. Participating centres included adult renal transplant recipients and 30-day follow-up data. The primary outcome was LOS. Multivariable hierarchical models compared cohorts. 213 patients were included in the study period. 18/23 UK kidney transplant centres were represented. Analysis of the perioperative care delivery demonstrated similar patterns irrespective of reported protocols, with a tendency towards ERAS-type care. Between cohorts, the incidence of complications were similar; formal ERAS 14.3%, ERAS informal 17.0%, no ERAS 12.6%; p = 0.64. Median LOS was also similar; formal ERAS 6.0~days (5.0–11.5), informal ERAS 7.0~days (5.0–10.5) vs. no ERAS 6.0~days (5.0–10.5); p = 0.75. Readmissions were comparable; p = 0.721. Multivariable models confirmed these findings and demonstrated frailer patients had longer LOS and more readmissions. Currently, most UK renal transplant centres deliver a form of peri-operative ERAS care, indicating broad adoption of ERAS principles. Consequently, a formal ERAS protocol is not associated with decreased complications, LOS or readmissions. Efforts to improve outcomes should focus on prehabilitation of at-risk groups on the waiting list.
2025
Causes of Prolonged Cold Ischemia Time After Arrival of Deceased Donor Kidney at Implanting Center: Results From a Prospective Audit
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ABSTRACT Background Deceased donor kidney transplants often face delays, leading to prolonged cold ischemia time (CIT), yet data on post-allograft arrival delays are scarce. Objectives This audit aims to identify and characterize the delays contributing to CIT prolongation after allograft arrival at the implanting center. Design Data was collected prospectively from 14 UK centers between February and September 2022. Timelines from allograft arrival to the implanting center to implantation were recorded for adult deceased donor kidney-only transplants. Results The median CIT for all 446 allografts [(donation after cardiac death (DCD), 48.2% and donation after brain death (DBD), 51.6%)] was 11:08 h (interquartile range (IQR): 08:15–15:12). A total of 42% of DCD and 15% of DBD allografts exceeded the national recommended duration of 12 and 18 h, respectively. CIT was prolonged in centers with dedicated transplant theaters, with a median CIT of 13:41 (IQR: 08:11–15:13) compared to a median CIT of 09:43 (IQR: 07:36–12:29) hours ( p < 0.005, 95% CI: -4.40, -2.60) in centers without dedicated transplant theaters. Compared to full cross-match (FXM) results, a higher proportion of Virtual cross-match (VXM) results (75.2%~vs. 89.4%, Odds Ratio (OR): 2.79, CI: 1.57–5.0, p < 0.005) were available before the allograft arrived at the implanting center. The proportion of crossmatch results available before the recipient’s arrival at the implanting center was 31.7% (46.6% for VXM vs. 4.9% for FXM, OR: 16.76, CI: 7.50, 44.17, p < 0.005). However, no difference was found in CIT between the VXM (median: 11:06, IQR: 08:14–15:20) and FXM (median: 11:00, IQR: 08:34–14:56) groups ( p = 0.75, CI: -0.75, 1.02). Qualitative analysis identified theater and staff unavailability as common reasons for delay. Conclusion Internal center practices have a significant impact on CIT, necessitating intervention to optimize transplant outcomes.
Evaluation of a National Digital Pre-Implantation Biopsy Service for Deceased-Donor Kidney Transplantation in the UK (Pithia Trial); a Stepped-Wedge Cluster Randomised Registry Trial
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Abstract
Background Pre-implantation biopsy may help select kidneys retrieved from elderly deceased donors for transplantation, but concerns persist that it may cause unnecessary discard of kidneys that would have provided acceptable transplant function. The PITHIA trial tested the hypothesis that introduction of a National Digital Pathology Service (NDPS) would increase the proportion of kidneys transplanted from elderly donors and/or improve their function.
2024
Quality Assurance in Surgical Trials of Arteriovenous Grafts for Haemodialysis: A Systematic Review, a Narrative Exploration and Expert Recommendations
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Abstract
BACKGROUND: Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability. It is essential, therefore, when considering an RCT of a novel surgical procedure or device that quality assurance (QA) is defined for both the new approach and the comparator. The aim of this systematic review was to evaluate the QA standards performed in RCT of AVG using a multi-national, multi-disciplinary approach and propose an approach for future RCT. METHOD: The methods of this have been previously registered (PROSPERO: CRD420234284280) and published. In summary, a four-stage review was performed: identification of RCT of AVG, initial review, multidisciplinary appraisal of QA methods and reconciliation. QA measures were sought in four areas - generic, credentialing, standardisation and monitoring, with data abstracted by a multi-national, multi-speciality review body. RESULTS: QA in RCT involving AVG in all four domains is highly variable, often sub-optimally described and has not improved over the past three decades. Few RCT established or defined a pre-RCT level of experience, none documented a pre-trial education programme, or had minimal standards of peri-operative management, no study had a defined pre-trial monitoring programme, and none assessed technical performance. CONCLUSION: QA in RCT is a relatively new area that is expanding to ensure evidence is reliable and reproducible. This review demonstrates that QA has not previously been detailed, but can be measured in surgical RCT of vascular access, and that a four-domain approach can easily be implemented into future RCT.
The Influence of Socioeconomic Deprivation on Outcomes in Transplant Patients Infected with SARS-CoV-2 in Wales
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INTRODUCTION: SARS-CoV-2 infection has had a significant impact on vulnerable individuals including transplant patients. Socioeconomic deprivation negatively affects outcomes of many health conditions. The aim of this study was to evaluate the effect of socioeconomic deprivation on the incidence and severity of SARS-CoV-2 infection among Welsh transplant patients. METHODS: This study is a retrospective, cross-sectional study on the transplant population of Wales. The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes of Welsh transplant patients who developed SARS-CoV-2 infection. Outcome measures were the incidence of SARS-CoV-2 infection, rates of hospital and ICU admission, development of acute kidney injury (AKI) and mortality. A logistic binomial regression analysis was used to correlate the various risk factors with the incidence of SARS-CoV-2 infection. RESULTS: Two hundred and sixty-six (25%) of regular follow up patients had SARS-CoV-2 infection; of these 55 (20.7%) were admitted, 15 (5.6%) to ICU, 37 (13.9%) developed AKI, and 23 (8.6%) died. In a regression analysis, patients of younger age were associated with more (p=.001) and those with SPK (simultaneous pancreas kidney) transplant less chance of infection (p=.038), whereas social deprivation was not associated with the chance of infection (p=.14). In regression analysis increased social deprivation was associated with higher chance of AKI post SARS-CoV-2 (p=.049). CONCLUSIONS: Socioeconomic deprivation did not affect the rates or severity of SARS-CoV-2 infection apart from the degree of AKI in Welsh Transplant patients. Adherence to the preventive measures for this high-risk population must continue to remain a priority.
2023
Quality Assurance in Surgical Trials of Arteriovenous Grafts for Haemodialysis: Protocol for a Systematic Review
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Abstract
INTRODUCTION: Decisions regarding the optimal vascular access for haemodialysis patients are becoming increasingly complex, and the provision of vascular access is open to variations in systems of care as well as surgical experience and practice. Two main surgical options are recognised: arteriovenous fistula and arteriovenous graft (AVG). All recommendations regarding AVG are based on a limited number of randomised controlled trials (RCTs). It is essential that when considering an RCT of a surgical procedure, an appropriate definition of quality assurance (QA) is made for both the new approach and the comparator, otherwise replication of results or implementation into clinical practice may differ from published results. The aim of this systematic review will be to assess the methodological quality of RCT involving AVG, and the QA measures implemented in delivering interventions in these trials. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify relevant literature. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data collected will pertain to generic measures of QA, credentialing of investigators, procedural standardisation and performance monitoring. Trial methodology will be compared against a standardised template developed by a multinational, multispecialty review body with experience in vascular access. A narrative approach will be taken to synthesise and report data. ETHICS AND DISSEMINATION: Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations, with the ultimate aim of providing recommendations for future RCT of AVG design.
Recruitment into Randomised Trials of Arteriovenous Grafts: A Systematic Review
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Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT. The most contentious and debated area of vascular access remains the role of arteriovenous grafts, and thus the quality of the data that is used to support opinions, guidelines and recommendations is critical. The aim of this review was to determine the extent of variation in the planning and recruitment in all RCT involving AVG. The findings of this are stark: there have been only 31 RCT performed in 31,years, the vast majority of which exhibited major limitations severe enough to undermine the results. This underlines the need for better quality RCT and data, and further inform the design of future studies. Perhaps most fundamental is the planning for a RCT that accounts for the intended population, the uptake of a RCT and the attrition for the significant co-morbidity in this population.
2022
Thymoglobulin versus Alemtuzumab versus Basiliximab Kidney Transplantation from Donors After Circulatory Death
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Introduction 3C, a study comparing alemtuzumab versus basiliximab induction immunosuppression in kidney transplants has shown lower acute rejection rate with alemtuzumab but same graft survival. Aim of the current study is to examine the effect of induction immunosuppression (thymoglobulin, alemtuzumab, basiliximab) on the outcome of kidneys after circulatory death (DCD). Methods Data of the 274 DCD patients of the 3C obtained from the sponsor was compounded with the 140 DCD patients who received thymoglobulin in a single centre with the same entry criteria as the 3C, giving 414 patients on three induction regimes. Results There were more male donors (p<0.05) and HLA-DR mismatched patients in the thymoglobulin group (p<0.001). Death-censored graft survival at 6-months was 98.6% in the thymoglobulin, 95.5% in alemtuzumab (p=0.08) and 95.7% in basiliximab group (p=0.09), and at 2-years 97.9% vs. 94.8% (p=0.13, HR 2.8, CI 0.7-10.9), vs. 94.3% (p=0.06, HR 3.5, 95% CI 0.9-13.6) respectively. 2-year overall graft survival was 95% in the thymoglobulin vs. 88% in alemtuzumab (unadjusted p=0.038, adjusted HR 2.4, 95% CI 0.99-5.9) and 91.4% in the basiliximab group (p=0.21). 2-years patient survival was numerically less in the alemtuzumab compared to thymoglobulin group (91.8% vs 97.1%
An Analysis of Serological Response and Infection Outcomes Following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 Vaccines in Kidney and Kidney-pancreas Transplants
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Abstract
Severe acute respiratory syndrome coronavirus 2 is associated with high mortality among transplant recipients. Comparative data that define humoral responses to the Oxford-AstraZeneca (AZ) and BNT162b2 (Pfizer-BioNTech) vaccines are limited. We recruited 920 kidney transplant patients receiving at least 1 dose of severe acute respiratory syndrome coronavirus 2 vaccine, excluding patients with virus pre-exposure. Serological status was determined with the COVID-SeroKlir ELISA (Kantaro-EKF Diagnostics). Patients with a corrected antibody level of <0.7 AU/mL were considered seronegative. Four hundred ninety-five AZ and 141 Pfizer patients had a sample analyzed after first dose and 593 after second dose (346 AZ versus 247 Pfizer). After first dose, 25.7% of patients seroconverted (26.6% AZ, 22.8% Pfizer). After second dose, 148 (42.8%) of AZ seroconverted compared with 130 (52.6%) of Pfizer (P = 0.02; hazard ratio, 1.48; 95% confidence interval, 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have significantly higher response than AZ patients (median 2.6 versus 1.78 AU/mL
2021
Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant
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Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. isrctn.org Identifier: ISRCTN63852508
A Multicenter Randomized Controlled Trial Indicates That Paclitaxel-Coated Balloons Provide No Benefit during Angioplasty of Arteriovenous Fistulas.
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The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded. Following successful treatment with a high-pressure balloon, 212 patients were randomized. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon. The primary endpoint was time to loss of clinically-driven target lesion primary patency. Primary analysis showed no significant evidence for a difference in time to end of target lesion primary patency between groups: hazard ratio 1.18 with a 95% confidence interval of 0.78 to 1.79. There were no significant differences for any secondary outcomes, including patency outcomes and adverse events. Thus, our study demonstrated no evidence that paclitaxel-coated balloons provide benefit, following standard care high-pressure balloon angioplasty, in the treatment of arteriovenous fistulas. Hence, in view of the benefit suggested by other trials, the role of paclitaxel-coated angioplasty balloons remains uncertain.
Induction with ATG in DCD Kidney Transplantation; Efficacy and Relation of Dose and Cell Markers on Delayed Graft Function and Renal Function
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Aim We aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy. Methods 140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome. Results Graft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p < 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01). Conclusion Thymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.
2020
Oxygenated versus Standard Cold Perfusion Preservation in Kidney Transplantation (COMPARE): A Randomised, Double-Blind, Paired, Phase 3 Trial
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Background Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. Methods This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO2), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. Findings Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m2 (SD 19·3) in the HMPO2 group versus 46·7 mL/min per 1·73m2 (17·1) in HMP (mean difference 3·7 mL/min per 1·73m2, 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO2 group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO2 (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). Interpretation HMPO2 of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO2 and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO2 were suggested by analysis of secondary outcomes. Funding European Commission 7th Framework Programme.
Arterio-Venous Fistula Surgery Can Be Safely Delivered in the COVID-19 Pandemic Era
2019
Prophylaxis of Wound Infections-antibiotics in Renal Donation (POWAR)
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Abstract
Background: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. Methods: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). Findings: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. Interpretation: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.
Older Donation After Circulatory Death Kidneys for Older Recipients: A Single-Center Experience
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Abstract
The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients.
2018
`Educational’ Deprivation Is Associated with PD Peritonitis
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BACKGROUND:Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion. METHODS:The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes. RESULTS:Peritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the ‘Education’ domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced ‘2 or more peritonitis’ episodes (p = 0.04) and were hospitalized for antibiotics (p = 0.02). CONCLUSION:This study has shown that patients who live in more ‘educationally’ deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.
2016
Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome
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Abstract
BackgroundReasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome.MethodsPatients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age.ResultsOver a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5–79) and 42 (range, 15–85) mL/min compared with SKT of 35 (range, 10–65) and 32 (range, 6–65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group.ConclusionsGraft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission.
MicroRNA-21 (miR-21) Expression in Hypothermic Machine Perfusate May Be Predictive of Early Outcomes in Kidney Transplantation
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Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117–1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.
[Favourable effects of kidney transplantation on vascular condition of patients: Potential prognostic significance of non-invasive measurement of arterial stiffness]
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Introduction: Development of atherosclerosis is accelerated in kidney transplant patients. Impaired metabolic pathways have complex effect on the arterial wall which can be measured by non-invasive techniques. Only few data are available on the change of stiffness parameters in the postoperative course. Therefore, in this study the authors analysed the stiffness parameters of kidney transplant recipients during the perioperative period. Aim: Non-invasive clinical trial of the arterial functional parameters in the early postoperative period. Method: Seventeen successful primary kidney transplant patients with uneventful postoperative period (8 females, 9 males; age, 46.16 ± 12.19 years) were involved in this short-term prospective longitudinal study. The authors analysed correlations between non-invasively assessed stiffness parameters (pulse wave velocity PWV, augmentation index - AIx). Stiffness parameters were measured with a TensioMed Arteriograph. These parameters were assessed before the transplantation, as well as 24 hours, 1 and 2 weeks after surgery under standard conditions. Results: It was found that PWV (p = 0.0075) and AIx (p = 0.013) improved significantly. There was no significant change in case of PP and the other monitored parameters. Serum creatinine decreased (p = 0.0008) and glomerular filtration rate increased significantly (p = 0.0005). Conclusions: Along with the available data in the literature, the findings suggest that kidney transplantation has a positive effect on the arterial function. Improvement can be detected non-invasively with Arteriograph in the early postoperative period. Orv. Hetil., 2016, 157(24), 956–963.
[First Outcomes, since Being Full Member of Eurotransplant. A Single Center Experience of Cadaveric Kidney Transplantation]
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Introduction: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. Aim: The authors retrospectively compared the trends. Method: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). Results: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m 2 increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. Conclusions: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards. Orv. Hetil., 2016, 157(24), 925–937.
2015
The Influence of Socioeconomic Deprivation on Early Outcomes in Vascular Access Surgery
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Abstract
Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, and often poorer outcomes for patients with such conditions. The influence of deprivation on outcomes following vascular access surgery has not previously been reported. The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes following 507 consecutive first upper limb arteriovenous (AV) fistulas from a single institution in the United Kingdom, performed between 2011 and 2014. The primary outcome measures were early failure and maturation into a working fistula. Four hundred and five (80%) patients had a patent AV fistula at the 2-week follow-up clinic. Three hundred and fifty-nine (71%) patients developed a functionally mature AV fistula as determined by clinical assessment and a Doppler scan. There were no differences in either early failure rates (p = 0.95) or maturation rates (p = 0.77) between the least and most deprived groups of patients. In conclusion, this study has shown that socioeconomic deprivation does not influence outcomes following vascular access surgery.
Pregnancy Management of Women with Kidney Transplantation
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Women with renal disease, besides many dysfunctions, face increasing infertility and high-risk pregnancy due to uremia and changes of the hormonal functions. After renal transplantation, sexual dysfunction improves, providing the possibility of successful pregnancy for women of childbearing age. However, kidney transplanted patients are high-risk pregnant patients with increased maternal and fetal risks, and the graft also may be compromised during pregnancy; most studies report on several successive deliveries due to multidisciplinary team management. In clinical practice, the graft is rarely affected during the period of gestation. Fetal development disorders are also rare although preterm delivery and intrauterine growth retardation are common. For now, several studies and clinical investigations proved that, under multidisciplinary control, kidney transplanted female patients are also possible to have safe pregnancy and successful delivery. There are conflicting data in the literature about the prevention of complications and the timing of pregnancy. Herein, we would like to present some experience of our centre. A total of 847 kidney transplantations have been performed between June 1993 and December 2013 with 163 childbearing aged females (18-45 years) in our center. We report on three kidney transplanted patients who have given birth to healthy newborns. In our practice, severe complications have not been observed.
2013
Prognosis of Dialysed Patients after Kidney Transplant Failure
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Abstract
Background/Aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18). Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant.
Effects of Tacrolimus on Action Potential Configuration and Transmembrane Ion Currents in Canine Ventricular Cells
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Abstract
Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3–30 \[M) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations \]3 $$M blocked a variety of ion currents, including ICa, Ito, IK1, IKr, and IKs. Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.
2011
Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Predicts Left Ventricular Hypertrophy After Renal Transplantation
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Abstract
BackgroundKidney transplant recipients show a higher risk for cardiovascular complications, such as left ventricular hypertrophy and heart failure, leading to the premature death in many cases.MethodsWe investigated the contribution of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to the development of left ventricular hypertrophy (LVH), an indicator of heart disease progression among kidney transplant recipients.ResultsWe observed a significant correlation between graft function and left ventricular mass index. The occurrence of LVH or severe LVH was significantly greater among patients with at least one D-allele (ID or DD).ConclusionThe use of ACE inhibitors or angiotensin receptor blockers seemed to be advantageous for patients with the ID and especially, the DD genotype.
Validation of a Prognostic Function for Renal Transplant Recipients in Hungary
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Abstract
Renal transplantation (RTx) is the treatment of choice for end-stage renal failure, but these patients are increasingly older and have additional conditions leading to high mortality after RTx. The aim of our study was to validate a Spanish prognostic function that estimates survival in Hungarian renal transplant recipients.
2010
Insertion/Deletion Polymorphism of Angiotensin-Converting Enzyme as a Risk Factor for Chronic Allograft Nephropathy
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Abstract
Angiotensin-converting enzyme (ACE) inhibitor therapy is widely used to treat chronic allograft nephropathy (CAN), which suggests a possible role of the renin-angiotensin system in the pathologic mechanism of the disease. The objective of this study was to investigate the possible link between CAN and ACE. The ACE insertion/deletion polymorphism and the amount and activity of ACE were determined in cadaver kidney recipients with CAN (n = 38) or normal renal function (n = 34). The DD genotype was observed significantly more frequently in the CAN group compared with the group with normal renal function. Moreover, the DD genotype was associated with a higher serum ACE concentration and greater serum ACE activity, compared with II genotype homozygotes. The insertion/deletion polymorphism of ACE affects ACE expression and activity in serum, and, therefore, may have an important role in the pathogenesis of CAN. These findings suggest that determination of the ACE genotype may be useful in identifying patients at high risk. In particular, the DD genotype may be considered an indication for ACE inhibitor therapy.
Arterial Stiffness in Chronic Renal Failure and After Renal Transplantation
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Abstract
Arterial stiffness is an independent cardiovascular risk factor, along with aging, hypertension, and cardiovascular disease. The augmentation index (AIx) and pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes. Arteriography was used to determine systolic and diastolic blood pressure, pulse pressure (PP), AIx, and PWV in 82 male and 64 female renal transplant recipients (mean [SD] age, 45.3 [11.2] years). Cardiovascular risk was assessed using echocardiography and ultrasonography of the carotid arteries. The left ventricular wall thickness, ejection fraction, and stenosis of the carotid arteries were also measured. Fasting serum creatinine, cystatin C, homocysteine, C-reactive protein, immunoreactive parathyroid hormone, lipid, and calcium-phosphorus concentrations were determined. The serum cystatin concentration was 2.1 (0.2) mg/L, and the homocysteine concentration, 15.2 (2.6) micromol/L. After transplantation, body mass index, fat mass, and visceral fat area increased significantly (P < .01). The AIx was increased (AIx > or =10%) in 20% of men and 37% of women, PWV was increased (>10 m/s) in 43% of men and 34% of women, and PP was pathologically high (>12 m/s) in 10% of men and 12% of women. The PWV was significantly related to age (r = 0.52) and ventricular wall thickness (r = 0.46). Pulse pressure, BMI, and systolic and diastolic blood pressure correlated positively but modestly with PWV. There was a significant relationship between AIx80 and systolic (r = 0.42) and diastolic (r = 0.39) blood pressure and PP (r = 0.33). The ejection fraction correlated negatively with PWV and AIx. There was a strong association between carotid artery stenosis, PWV, and AIx80. All patients with PWV greater than 10 m/s demonstrated carotid artery stenosis. In conclusion, arteriography is an objective, noninvasive, and convenient method for early diagnosis and follow-up of atherosclerosis.
Effect of Tacrolimus on the Excitatory Synaptic Transmission Between the Parallel Fibers and Pyramidal Cells in the Rat Dorsal Cochlear Nucleus
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Abstract
Aim The immunosuppressive drug tacrolimus has several effects on the central nervous system. Besides its protective effect in hearing deficiencies, it is also considered to be able to cause tinnitus. In the present work, we attempted to describe its effects on a characteristic synapse of the auditory system that may be involved in the pathogenesis of tinnitus. Methods/materials Slices of the dorsal cochlear nucleus (200 \[m thick) were prepared from 9- to 14-day-old Wistar rats. In response to stimulation targeting the superficial layer of the nucleus, we recorded excitatory postsynaptic currents (EPSCs) developing in the cell bodies of the pyramidal neurons using whole-cell voltage clamps. Inhibitory synaptic activity was inhibited by the application of bicuculline and strychnine. Short-term plasticity was investigated using high-frequency stimulation (50 Hz). Unambiguous identification of the investigated neurons was ensured by employing biocytin in the pipette solution, which allowed the confocal reconstruction of the cells after the functional measurements. A concentration of 1 \]mol/L tacrolimus was applied extracellularly. Results Tacrolimus effectively and reversibly inhibited glutamatergic neurotransmission in the investigated synapse from -145 ± 26 pA to -55 ± 15 pA (n = 7; P = .00928). In contrast, EPSC amplitudes without failures were not significantly reduced (from -153 ± 26 pA to -131 ± 23 pA) in the presence of tacrolimus, but there were increased failure numbers of synaptic transmission. These data suggested that application of tacrolimus produced a combined pre- and postsynaptic inhibition. Conclusion Tacrolimus affected short-term synaptic plasticity in the rat dorsal cochlear nucleus. It was also capable of inhibiting the glutamatergic neurotransmission. These effects suggested that tacrolimus may have neuroprotective effects in this structure.
2006
Renal Artery Aneurysm at the Anastomosis After Kidney Transplantation
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Abstract
Vascular complications represent serious problems after kidney transplantation. An aneurysm of the transplanted renal artery is an extremely rare but potentially devastating complication that which occurs in fewer than 1% of recipients. It can cause hypertension, functional impairment, and even graft loss. A 49-year-old man was admitted 6 months after his second renal transplantation. Duplex ultrasonography demonstrated an aneurysm at the anastomosis of the transplanted renal artery. The patient has not had any complaints. The function of the graft was stable. A computed tomography scan confirmed the diagnosis. Because of the high risk of rupture we decided upon surgical repair. During the operation, blood flow to the kidney was occluded; the graft was cooled with Euro-Collin’s solution and ice-cold saline. After the resection there was enough usable arterial wall to construct a new anastomosis. The patient had an uneventful postoperative period, the serum creatinine decreased to the preoperative level, and the function of the graft was stable. Renal artery aneurysms represent high-risk complications. We decided on surgical repair, which was performed with simultaneous perfusion and cooling of the graft. There are only a few similar cases in the literature; it was the first operation using this method in our practice. Surgical reconstruction of a renal artery aneurysm, if feasible, is a safe procedure that prevents aneurysm rupture and saves the graft.
2001
[Acute Pancreatitis after Kidney Transplantation].
PubMed
Abstract
Pancreatitis following kidney transplantation was first described by Starzl in 1964 [19].The incidence rate of the disease involving severe complications ranges from 1.2 to 6.8%. The number of risk factors, besides those of the normal population, is increased by a number of other factors, i.e. uremia, disorder of lipid metabolism, polycystic kidney, immunosuppressive drugs, cytomegalovirus infection, etc. The mortality of acute pancreatitis in a kidney transplant patient is, in spite of treatment with the most up-to-date methods, is much higher (53–60%) than that for a non-transplant patient. In the period between 27 June 1991 and 31 December 2000 the number of cadaver kidney transpants performed in the Transplantation Division of the 1st Department of Surgery of the Medical and Health-Science Centre of the University of Debrecen was 349. During this period 9 incidences of acute pancreatitis were found in 8 patients. The frequency of incidence was 2.56%. In the present communication we analyse the prognosis of 9 kidney transplant patients, with special respect to immunosuppression. Risk fators: One patient was administered Cyclosporin alone, four were given Cyclosporin and Steroids, a further one Cyclosporin, Steroids and Azathioprine, the remaining three were treated with Cyclosporin, steroids and Mycophenolate Mophetil. In six cases out of nine multiorgan insufficiency (kidney, lung, liver) was encountered on presentation, three cases were accompanied by peritonitis. In spite of early jejunal nutrition, intensive therapy, antibiotic treatment, CT monitoring, if needed, necrectomy and oncotomy, three of our patients died from multiorgan insufficiency induced by septico-toxic state (mortality 33.3%). Other six patients recovered. Conclusions: the mortality rate of acute pancreatitis is much higher in immunosuppressed patients. The role of the etiological factors is not unequivocal in the development of pancreatitis. Nevertheless, all possible risk factors have to be taken into consideration when starting the immunosuppressive treatment of transplant patients and during their follow-up. By optimally adjusting the immunosuppressants we can decrease the risk of pancreatitis, however, the prognosis of the disease, in agreement with the data in the literature, cannot be considerably improved even with the most up-to-date methods.