Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
The aim of this systematic review was to examine the role of blood pressure lowering agents in transplant patients with a functioning kidney allograft. A large number of studies were included (94 studies), including a total of 7547 adults, all of which were randomised controlled studies. The authors found that none of the blood pressure-lowering agents reduced the risk of graft loss nor did they show significant differences in terms of all-cause death, cardiovascular death and withdrawal because of adverse events, in comparison to placebo or other drug class. Although only RCTs were included, some of them were of poor quality and/or were publish over 20 years ago—these factors may have influenced the certainty of the findings. This study also highlights the insufficient reporting of data on important variables such as donor type (living versus deceased), time after transplantation and quality of life, which may have restricted the authors from performing a more granular analyses of the outcomes. Hence, the authors concluded that the evidence basis for this topic is poor that cannot be used to inform clinical decision-making.
Aims:
This study aimed to assess the benefits and harms associated with blood pressure lowering agents in renal transplant recipients with a functioning graft.
Interventions:
Three electronic databases including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Two reviewers independently selected studies for inclusion and extracted data. The Cochrane Risk of Bias Tool was used to assess the risk of bias.
Participants:
94 studies were included in the review.
Outcomes:
The primary effectiveness outcome was graft loss, and safety outcome was withdrawal due to adverse events. The secondary outcomes were death (all-cause and cardiovascular), cardiovascular disease, acute rejection, acute kidney injury, acute dialysis, estimated glomerular filtration rate (eGFR), creatinine clearance, systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), adverse events and quality of life.
Follow Up:
N/A
OBJECTIVE:
Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant.
METHODS:
We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis.
RESULTS:
Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively).
CONCLUSION:
The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
CMV infection which is refractory to standard treatment is a challenging clinical problem, resulting in patient morbidity and increased healthcare costs, mainly due to prolonged and repeat admissions. In the SOLSTICE trail, Maribavir was shown to be more effective than standard treatment protocols for refractory CMV infection in post-transplant patients. This post-hoc analysis of the SOLISTICE trial used trial data to calculate the reduction in healthcare costs that could be achieved by using Maribavir in this patient population. The analysis demonstrated a third to two thirds reduction in costs over an 8-week period when using Maribavir. Healthcare cost analyses are complex and subject to many assumptions, which the authors acknowledge introduces significant bias. However, the most striking omission from the analysis is the cost of the Maribavir treatment itself, which is significantly higher than standard therapy. With the additional limitation of a short duration of study, the reliability and applicability of the reported cost savings cannot be readily determined.
Aims:
The aim of this study was to use the data from the randomised controlled trial, SOLSTICE, to estimate the cytomegalovirus (CMV) related health care resource utilization (HCRU) costs of maribavir (MBV) versus investigator-assigned therapy (IAT), among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients.
Interventions:
Participants in the SOLSTICE trial were randomised to either receive IAT or MBV therapy.
Participants:
352 patients that had either HSCT (40%) or SOT (60%).
Outcomes:
The key outcomes were the cost of hospitalisation with IAT versus MBV therapy, and cost difference (i.e. cost savings) with MBV.
Follow Up:
N/A
BACKGROUND:
Cytomegalovirus (CMV) infections among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients impose a significant health care resource utilization (HCRU)-related economic burden. Maribavir (MBV), a novel anti-viral therapy (AVT), approved by the United States Food and Drug Administration for post-transplant CMV infections refractory (with/without resistance) to conventional AVTs has demonstrated lower hospital length of stay (LOS) versus investigator-assigned therapy (IAT; valgancilovir, ganciclovir, foscarnet, or cidofovir) in a phase 3 trial (SOLSTICE). This study estimated the HCRU costs of MBV versus IAT.
METHODS:
An economic model was developed to estimate HCRU costs for patients treated with MBV or IAT. Mean per-patient-per-year (PPPY) HCRU costs were calculated using (i) annualized mean hospital LOS in SOLSTICE, and (ii) CMV-related direct costs from published literature. Probabilistic sensitivity analysis with Monte-Carlo simulations assessed model robustness.
RESULTS:
Of 352 randomized patients receiving MBV (n = 235) or IAT (n = 117) for 8 weeks in SOLSTICE, 40% had HSCT and 60% had SOT. Mean overall PPPY HCRU costs of overall hospital-LOS were $67,205 (95% confidence interval [CI]: $33,767, $231,275) versus $145,501 (95% CI: $62,064, $589,505) for MBV and IAT groups, respectively. Mean PPPY ICU and non-ICU stay costs were: $32,231 (95% CI: $5,248, $184,524) versus $45,307 (95% CI: $3,957, $481,740) for MBV and IAT groups, and $82,237 (95% CI: $40,397, $156,945) MBV versus $228,329 (95% CI: $94,442, $517,476) for MBV and IAT groups, respectively. MBV demonstrated cost savings in over 99.99% of simulations.
CONCLUSIONS:
This analysis suggests that Mean PPPY HCRU costs were 29%-64% lower with MBV versus other-AVTs.
Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This is a very interesting, novel, RCT in heart transplantation. Heart recipients were randomised to standard care or to receive additional therapy with intra-operative hemoadsorption with the Cytosorb system from CytoSorbents, NJ, USA. The hemoadsorption cartridge was integrated into the cardiopulmonary bypass system and has been shown previously to remove cytokines, chemokines, bilirubin, myoglobin and plasma free haemoglobin. Patients were blinded to the treatment allocation, but clinical professionals were not. No sample size calculation could be done due to a lack of prior data on which to base it. The study found statistically significant differences across a range of outcomes, including the primary outcomes. Patients receiving hemoadsorption had a lower vasoactive-inotropic score, frequency of vasoplegic syndrome, risk of AKI, shorter median mechanical ventilation and median intensive care stay (by 3.5 days). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups, although it may have been too small to show differences in these outcomes. There were no device related complications.
Aims:
This study aimed to investigate the role of intraoperative haemoadsorption in orthotopic heart transplant patients.
Interventions:
Participants were randomised to receive either intraoperative haemoadsorption or standard care.
The primary endpoint was early post-operative haemodynamic instability. Secondary endpoints were changes in procalcitonin (PCT) and C-reactive protein (CRP) levels post-operation, intraoperative change in mycophenolic acid (MPA) concentration, early allograft rejection, frequency of post-operative organ dysfunction, adverse immunological events, major complications, duration of ICU and in-hospital stay, and 1-year survival.
Follow Up:
1 year
AIMS:
The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT).
METHODS AND RESULTS:
In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] μg/mL vs. 1.6 [1.20-3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] μg/mL vs. 0.9 [0.45-2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups.
CONCLUSIONS:
Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
Hepatorenal syndrome (HRS) resulting in renal dysfunction results in poorer outcomes following liver transplantation (LT). The efficacy of Terlipressin in reducing HRS in liver failure patients was investigated in the CONFIRM trial, which showed significantly improved rates of HRS, but no difference in mortality at 90 days. This post-hoc analysis of the CONFIRM trial aimed to determine the difference in renal outcomes (pre and post LT) and 1-year survival in patients who had Terlipressin versus those who did not. The analysis found significant improvements in renal outcomes and 1-year survival in the Terlipression group. However, sub-group analysis showed that patients with more severe liver and renal disease showed poorer outcomes with terlipressin use, indicating a need for careful patient selection. Further trials will be required to better define the patient sub-group that will derive the most benefit from Terlipressin therapy.
Aims:
This post hoc analysis of the CONFIRM trial aimed to examine whether terlipressin was effective in reducing the need for renal replacement therapy (RRT) and improving posttransplant outcomes in liver transplant recipients.
Interventions:
Particpants in the CONFIRM trial were randomised to receive either terlipressin plus albumin or placebo.
Participants:
300 liver transplant recipients from the CONFIRM trial.
Outcomes:
The main outcomes of interest were the incidence of hepatorenal syndrome-type 1 (HRS-1) reversal, need for RRT (pretransplant and posttransplant), and overall survival.
Follow Up:
12 months
Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This systematic review synthesised the available data reporting on the rate and associated risk factors of incisional hernia (IH) after renal transplantation. The authors report on pooled results which are broadly similar to that of other surgical groups, with obesity, smoking and immunosuppression reported as the main risk factors for the development of IH. There are a number of fundamental errors in the statistical analysis. For example, forest plots are used inappropriately to depict cross-sectional data, and the risk of bias tool was modified by the authors resulting in all included studies being rated as ‘good’ or ‘very good’.
Aims:
This study aimed to summarise the current literature on rates, risk factors and outcomes of incisional hernias following renal transplantation.
Interventions:
Electronic databases including PubMed, EMBASE and the Cochrane CENTRAL were searched. Studies were selected independently by two reviewers and data were extracted independently by three reviewers. Risk of bias was assessed using a modified Newcastle–Ottawa scale.
Participants:
20 studies were included in the review.
Outcomes:
The primary outcome was rates of IH. Secondary outcomes included risk factors for IH, and management and outcomes of IH.
Follow Up:
N/A
PURPOSE:
Incisional hernia (IH) post renal transplant (RT) is relatively uncommon and can be challenging to manage clinically due to the presence of the kidney graft and patient immunosuppression. This systematic review and meta-analysis synthesises the current literature in relation to IH rates, risk factors and outcomes post RT.
METHODS:
PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched up to July 2023. The most up to date Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were followed. Pertinent clinical information was synthesised. A meta-analysis of the pooled proportions of IH rates, the rates of patients requiring surgical repair and the rates of recurrence post RT are reported.
RESULTS:
Twenty studies comprising 16,018 patients were included in this analysis. The pooled rate of IH occurrence post RT was 4% (CI 3-5%). The pooled rate of IH repair post RT was 61% (CI 14-100%). The pooled rate of IH recurrence after repair was 16% (CI 9-23%). Risk factors identified for IH development post RT are BMI, immunosuppression, age, smoking, incision type, reoperation, concurrent abdominal wall hernia, lymphocele formation and pulmonary disease.
CONCLUSIONS:
IH post RT is uncommon and the majority of IH post RT are repaired surgically on an elective basis.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
There is considerable variation in the use of intraoperative vasoactive drugs in liver transplantation. This network meta-analysis attempted to synthesise the available data comparing outcomes - primarily rate of acute kidney injury (AKI) - between different vasoactive drug protocols utilised in liver transplantation. 25 trials were included in the analysis, and the effect of vasoconstrictor-, somatostatin infusion- and vasodilator - based strategies were compared. The quality of evidence of the included trials was generally low, and differences in outcome definition and inconsistent reporting of confounding factors made data synthesis which reached meaningful conclusions difficult. Unsurprisingly, no significant differences in effect on the primary outcome between the varies vasoactive drugs were found in this systematic review. Terlipressin was highlighted as its benefit in reducing AKI in liver failure patients with hepatorenal syndrome and in patients with septic shock is well established. The authors argued that this implies that terlipressin could confer a similar benefit in liver transplantation and warrants further study. However, the difficulties encountered in this review highlights that the confounding effects of donor and patient factors would require any such trial to have a large sample size to be sufficiently powered to detect a significant effect.
Aims:
This study aimed to assess the role of vasoactive agents versus any other drug, placebo, or standard of care on acute kidney injury (AKI) or other perioperative outcomes among adult liver transplant recipients.
Interventions:
Electronic databases including MEDLINE (Ovid), CINAHL (EBSCOhost), EBM Reviews (Ovid), EMBASE (Ovid), PubMed, and Google Scholar were searched. Three reviewers performed study screening and selection, and two reviewers independently extracted data. The Cochrane risk of bias (RoB) assessment tool version 2.0 was used to assess the risk of bias.
Participants:
25 studies were included in the review.
Outcomes:
The main outcomes of interest included acute kidney injury (AKI), intraoperative blood loss, graft complications, cardiovascular complications, pulmonary complications, infectious complications other than pneumonia, neurological complications, duration of mechanical ventilation, intensive care unit and hospital length of stay, and hospital mortality.
Follow Up:
N/A
We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This interesting randomised trial aimed to investigate the effect of internal iliac artery (IIA) versus eternal iliac artery (EIA) anastomosis on sexual function after kidney transplantation. It is thought that IIA anastomoses reduce blood flow to the genital tract, but previous retrospective work comparing these techniques found no significant difference in sexual function. 112 patients were included and completed a standardised erectile function questionnaire before- and one year after kidney transplant. The investigators found similar scores for overall sexual satisfaction but poorer scores for erectile function in the IIA group. Although not formally part of the analysis, the authors reported two cases of ureteric leaks in the IIA group and posited that IIA also confers an increased risk of ureter-vesical anastomosis leak. This further supports the conclusion that EIA should be the technique of choice for kidney transplantation.
Aims:
The aim of this study was to investigate the effect of internal versus external iliac artery anastomosis on sexual function in kidney transplant recipients.
Interventions:
Participants were randomly assigned to either the internal iliac anastomosis group and the external iliac artery anastomosis group.
Participants:
122 sexually active male renal transplant recipients.
Outcomes:
The primary outcome was the assessment of sexual function posttransplantation using the Persian version of the International Index of Erectile Function-15 questionnaire (IIEF-15) questionnaire.
Follow Up:
1 year
PURPOSE:
The choice between using the internal or external iliac arteries to supply a transplanted kidney poses a dilemma during renal transplantation. As the internal iliac artery branches to the genital tract, cutting it could potentially result in sexual dysfunction. The purpose of this study was to compare the effects of these two surgical methods on sexual function.
MATERIALS AND METHODS:
122 sexually active male patients under the age of sixty were randomly divided into two groups: the internal iliac anastomosis group and the external iliac artery anastomosis group. Before surgery and one year after the procedure, patients completed the International Index of Erectile Function-15 questionnaire (IIEF- 15), and the difference in scores of each domain was measured.
RESULTS:
Statistically, kidney transplantation improved all domains of IIEF in both groups, except for erectile function in patients who underwent internal iliac artery anastomosis group. Additionally, there were significant differences between the two groups in the domains of erectile function (p-value=0.04) and overall satisfaction (p-value = 0.002), while other domains such as orgasmic function, sexual desire, and intercourse satisfaction did not show any statistically significant differences.
CONCLUSION:
In conclusion, the choice between using the internal or external iliac artery for arterial anastomosis during kidney transplantation does not significantly impact graft function. However, it may negatively affect erectile function in patients who undergo internal iliac artery anastomosis.
Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This systematic review aimed to investigate the available endourological options for the treatment of ureteral stricture following renal transplantation. A total of 19 studies were included, all of which were retrospective in nature--this is likely to have introduced bias. No meta-analysis was performed due to heterogeneity between studies, and absence of randomised controlled trials and standardised outcomes. While the variability among studies and limitations in data provided regarding use of antegrade or retrograde approaches as well as robotic approaches means that it is difficult to draw firm conclusions; nevertheless, the authors conclude that minimally invasive endourological techniques are safe and show long-term benefits and can therefore be used as the first-line treatment of ureteral stricture in patients with renal transplant. Since success rates are influenced by factors such as the specific technique used, the timing of diagnosis and intervention, and the characteristics of the ureteral stricture, the authors recommend establishing a classification system which may help in choosing the best treatment approach. Additionally, developing standardised protocols and conducting research with a prospective design may help in addressing knowledge gaps.
Aims:
This study aimed to explore the different endourological treatment options for treating ureteral stricture in renal transplant patients.
Interventions:
Five electronic databases were searched, including EMBASE, MEDLINE, SCOPUS, Google scholar and the Cochrane library. Two independent reviewers selected studies for inclusion and extracted data. The methodological quality of the included studies was assessed using the RoB 2 and ROBINS – I tools.
Participants:
19 studies were included in the review.
Outcomes:
The main outcomes of interest included identification of techniques to resolve hydronephrosis or to treat ureteral stricture, their success rate and complications.
Follow Up:
N/A
Purpose: To analyze the utility and outcomes of available endourologic options to treat ureteral stricture after kidney transplantation (KT). Methods: A systematic review was carried out for all English language articles from 2000 to 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards using EMBASE, MEDLINE, SCOPUS, Google scholar, and Cochrane library. The search term combination for the string was follows: [(Ureteral stricture) OR (ureter stenosis) OR (ureteral stenosis) OR (Stricture ureter) OR (Narrowing ureter) OR (Ureter restriction) OR (ureteral restriction) OR (ureteral narrowing) OR (ureteral obstruction) OR (ureter obstruction) OR (obstructing ureter) OR (obstructive ureter) OR (narrow ureter) OR (ureteral narrow)] AND [(kidney transplant) OR (transplanted kidney) OR (transplant) OR (transplantation)] AND [(management) OR (Robotic) OR (laser) OR (stent) OR (dilatation) OR (dilation) OR (endoscopic) OR (endourological) OR (Urologic) OR (laparoscopic) OR (surgery) OR (treatment)]. Case reports, review articles, animal and laboratory studies were excluded. Risk of bias assessment was conducted using the RoB 2 and ROBINS-I tools. Results: A total of 1102 relevant articles published from 2000 to 2023 were found. After screening of titles and abstracts, a total of 19 articles were included in our systematic review. Ureteral stent/nephrostomy placement, balloon dilatation (ureteroplasty) with or without laser was used as initial approaches whereas follow-up and success rate were analyzed among other parameters. Conclusions: The management of ureteral strictures after KT is challenging and selecting the most appropriate treatment is crucial for successful outcomes. Our review suggests that, an endourologic management is a safe option with good long-term outcomes, especially in short and early strictures.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This pilot study recruited lung transplant recipients at 2 sites, and randomised them to standard immunosuppression (Tac, MMF, Pred) or a belatacept-based regimen (Tac, Belatacept and pred). The hypothesis was that belatacept-based immunosuppression might reduce the incidence of donor-specific antibodies (DSA), leading to a reduction in the risk of chronic lung allograft dysfunction (CLAD). The study was stopped after recruitment of 27 patients due to 3 deaths in the belatacept arm. Causes of death varied – 2 patients died from COVID-19 infection, one from CLAD related to infection, one from PTLD, one from pulmonary embolus and one from haemothorax. The authors ascribe 4 of these deaths to viral infections. No differences were seen in incidence of CLAD or development of DSA. It is very difficult to interpret these results given the small numbers, but clearly the authors were correct in stopping the study and switching patients to standard immunosuppression. The relationship of four of the deaths to viral infection would suggest that the immunosuppressive regimen may have contributed, and in the absence of any detectable clinical benefit, the conclusion that this regimen is unsafe in lung transplant recipients seem justified.
Aims:
This study aimed to evaluate the feasibility and inform the design of an RCT investigating the efficacy and safety of belatacept following lung transplantation
Interventions:
Participants were randomly assigned to either continue standard-of-care immunosuppression or switch to belatacept.
Participants:
27 lung transplant recipients.
Outcomes:
The primary outcome was to assess the feasibility of randomising 80% of eligible patients within 4 hours posttransplantation. The primary outcome was later changed to survival following the cessation of treatment with belatacept.
Follow Up:
1 year posttransplantation.
BACKGROUND:
Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.
METHODS:
We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.
RESULTS:
After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.
CONCLUSIONS:
We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
Hepatocyte growth factor has cytoprotective and anti-apoptotic effects in renal epithelial cells and has been shown to reduce renal dysfunction in animal models of renal injury. This phase 3, multicentre, double blind RCT investigated the use of ANG-3777 in deceased donor transplant recipients with delayed graft function. Use of the hepatocyte growth factor mimetic did not result in any differences in clinical outcomes, including dialysis requirement, acute rejection or graft function. The study is well designed with adequate blinding and randomisation. It should be noted that the study population was largely (>80%) DBD donors with a mean age of 44, and included around 35% kidneys undergoing hypothermic machine preservation, which may have impacted baseline DGF rates compared to a population with higher DCD or SCS subgroups and potentially represent less injured kidneys. Whether ANG-3777 has a role to play in more injured (e.g. ECD, DCD) kidneys remains unclear.
Aims:
The aim of this study was to investigate the effect of ANG-3777 in deceased donor renal transplant recipients with delayed graft function (DGF).
Interventions:
Participants were randomised to either the ANG-3777 group or the placebo group.
Participants:
253 deceased kidney transplant recipients.
Outcomes:
The original primary outcome was changed from duration of dialysis through day 30 to estimated glomerular filtration rate (eGFR) at day 360 posttransplant. The main secondary outcome was the severity of DGF.
Follow Up:
360 days posttransplantation
In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.
CET Conclusion