Transplant Library

Transplant Evidence Alert

The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).
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March 2023

Kidney
A Systematic Review and Meta-Analysis of Posttransplant Anemia With Overall Mortality and Cardiovascular Outcomes Among Kidney Transplant Recipients
  • Mekraksakit P
  • Leelaviwat N
  • Benjanuwattra J
  • Duangkham S
  • Del Rio-Pertuz G
  • et al.
Prog Transplant. 2023 Mar;33(1):78-89 doi: 10.1177/15269248221145046.
CET Conclusion
Reviewer: Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review aimed to assess the impact of posttransplant anaemia (PTA) on overall mortality, graft loss and cardiovascular outcomes. Two electronic databases were used to conduct the literature search. Study screening and data extraction were performed in duplicate. A total of 17 studies were included, all of which were observational cohort studies. The authors concluded that kidney transplant recipients (KTRs) with PTA had a significantly higher risk of overall mortality, graft loss, cardiovascular death and major adverse cardiovascular events (MACE), in comparison to KTRs without PTA. Heterogeneity was significant for some of the outcomes, which the authors speculated were due to differences in demographics, study design, and in definitions and onsets of PTA in each study. No attempts were made to adjust for the effect of confounders in the analysis.
Study Details
Aims: This study aimed to investigate the outcomes associated with posttransplant anaemia (PTA) in kidney transplant recipients.
Interventions: Electronic databases including MEDLINE and EMBASE were searched. Study selection and data extraction were performed by two independent reviewers. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale.
Participants: 17 studies were included in the review.
Outcomes: The primary outcomes were cardiovascular death and major adverse cardiovascular events (MACE). The secondary outcomes included overall mortality and graft loss.
Follow Up: N/A

Introduction: Posttransplant anemia is a common finding after kidney transplantation. A previous meta-analysis reported an association between anemia and graft loss. However, data on cardiovascular outcomes have not yet been reported. Objective: We conducted an updated meta-analysis to examine the association between posttransplant anemia and outcomes after transplantation including cardiovascular mortality in adult kidney transplant recipients. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2021. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios and 95% CIs. Results: Seventeen studies from August 2006 to April 2019 were included (16 463 kidney transplantation recipients). Posttransplant anemia was associated with overall mortality (pooled risk ratio = 1.72 [1.39, 2.13], I2 = 56%), graft loss (pooled risk ratio = 2.28 [1.77, 2.93], I2 = 94%), cardiovascular death (pooled risk ratio = 2.06 [1.35, 3.16], I2 = 0%), and cardiovascular events (pooled risk ratio = 1.33 [1.10, 1.61], I2 = 0%). Early anemia (≤6 months), compared with late anemia (>6 months), has higher risk of overall mortality and graft loss with a pooled risk ratio of 2.63 (95% CI 1.79-3.86; I2 = 0%) and 2.96 (95% CI 2.29-3.82; I2 = 0%), respectively. Discussion: In addition to increased risk of graft loss, our updated meta-analysis demonstrated that posttransplant anemia was significantly associated with poor outcomes after kidney transplantation including overall mortality, graft loss, cardiovascular death, and cardiovascular events. Future studies are required to assess the effects of treatment strategies for posttransplant anemia on posttransplant outcomes including cardiovascular mortality.
Outcomes of live renal donors with a history of nephrolithiasis; A systematic review
  • Bin Mohamed Ebrahim ME
  • Singla A
  • Yao J
  • Laurence JM
  • Wong G
  • et al.
Transplant Rev (Orlando). 2022 Dec 23;37(1):100746 doi: 10.1016/j.trre.2022.100746.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review explores the published data regarding living kidney donors with a history of renal stones. The authors identified 14 studies of 432 patients, identifying just one patient with a reported stone-related event. However, the identified studies were limited in quality and detail, and the average follow-up was just 21.1 months. Review methodology is good, with protocol registration, thorough literature search strategies and quality assessment. The authors make the best of the literature available with a comprehensive and well-written summary, but as they point out, there is significant risk of publication bias and under-reporting. More robust long-term registry data is required to truly quantify the risk to donors with existing stone disease.
Study Details
Aims: This study aimed to investigate the outcomes of kidney donors with a prior history of nephrolithiasis following donation.
Interventions: A literature search was conducted on Ovid and Embase. Eligible studies were selected by two independent reviewers. The Newcastle-Ottawa scale was used to assess the quality of the included studies.
Participants: 14 studies were included the review.
Outcomes: The primary outcome was stone-related event including stone-formation following donation, stone-induced obstruction, acute renal failure and sepsis. The secondary outcomes included short-term (≤30 days) and long-term (≥12 months) renal function.
Follow Up: N/A

The clinical outcomes of kidney donors with a prior history of nephrolithiasis are poorly defined. We conducted a systematic review assessing the post-donation clinical outcomes of kidney donors with a history of nephrolithiasis. Electronic databases (Ovid and Embase) were searched between 1960 and 2021 using key terms and Medical Subject Headings (MeSH) - nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Primary outcome was donor stone-related event. Secondary outcomes were renal function upon follow-up or post-operative nephrectomy complications. In summary, 340 articles were identified through database search. We identified 14 studies (16 cohorts) comprising 432 live donors followed up for a median of 26 months post live kidney donation. Six donors donated the stone-free kidney whilst 23 live donors had bilateral stones. Mean stone size was 4.2 ± 1.4 mm (1-16) with average follow up duration of 21.1 months (1-149). Twelve studies provided primary outcome (n = 138 patients) and eight (n = 348) for secondary outcomes. One donor had a stone-related event upon follow up. A total of 195 patients had eGFR <60 upon follow up. However, they were not significantly different when compared to renal function of live donors that didn't have pre-donation nephrolithiasis. Many of the studies couldn't provide long term follow up, coupled with limited data regarding the nature of the pre-donation stone disease. In conclusion, this systematic review shows that we have very limited information upon which to base recommendation regarding pre-donation risk of post-donation complications. Longer term follow up is required and lifelong follow up with live donor registries will aid further understanding.
Early calcineurin-inhibitor to belatacept conversion in steroid-free kidney transplant recipients
  • Tawhari I
  • Hallak P
  • Bin S
  • Yamani F
  • Safar-Boueri M
  • et al.
Front Immunol. 2022 Dec 19;13:1096881 doi: 10.3389/fimmu.2022.1096881.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small single-centre study randomised kidney transplant recipients with early steroid withdrawal three months post-transplant to one of three immunosuppressive regimens – Belatacept and MPA, Belatacept and low-dose tacrolimus, or Tacrolimus and MPA. In keeping with previous studies, the acute rejection rate was high in the belatacept/MPA arm, which was discontinued. Outcomes in the other two arms were statistically similar. The study is underpowered, with only 27 patients recruited across the three arms, and so any real conclusions are difficult to make. No sample size calculation is reported, and the original study protocol suggests planned recruitment of 43 patients. Significantly more patients would be required to show a clinically meaningful difference in the primary endpoint of change in eGFR. Of interest, 395 patients were screened for recruitment with only 27 patients consented and enrolled. Inclusion/exclusion criteria were not particularly restrictive, and no explanation is provided as to why recruitment rates were so poor.
Study Details
Aims: This study aimed to investigate the impact of early tacrolimus to Belatacept (Bela) conversion for maintenance immunosuppressive therapy in kidney transplant recipients.
Interventions: Participants were randomised to convert to Bela+mycophenolate (MPA), Bela+low dose Tac or to continue with Tac+MPA.
Participants: 27 kidney transplant recipients.
Outcomes: The primary outcome was the estimated glomerular filtration rate (eGFR). The secondary outcomes were patient survival, graft survival, incidence of de novo donor specific antibodies (DSA), incidence of biopsy proven acute rejection (BPAR), and incidence of adverse events such as posttransplant diabetes mellitus, infections, malignancies, and hyperlipidemia.
Follow Up: 24 months
BACKGROUND:

Belatacept (Bela) was developed to reduce nephrotoxicity and cardiovascular risk that are associated with the chronic use of Calcineurin inhibitors (CNIs) in kidney transplant recipients. The use of Bela with early steroid withdrawal (ESW) and simultaneous CNI avoidance has not been formally evaluated.

METHODS:

At 3 months post-transplant, stable kidney transplant recipients with ESW on Tacrolimus (Tac) + mycophenolate (MPA) were randomized 1:1:1 to: 1) Bela+MPA, 2) Bela+low-dose Tac (trough goal <5 ng/mL), or 3) continue Tac+MPA. All patients underwent surveillance graft biopsies at enrollment and then at 12, and 24 months post-transplant. Twenty-seven recipients were included; 9 underwent conversion to Bela+MPA, 8 to Bela+low-dose Tac and 10 continued Tac+MPA. Serial blood samples were collected for immune phenotyping and gene expression analyses.

RESULTS:

The Bela+MPA arm was closed early due to high rate of biopsy proven acute rejection (BPAR). The incidence of BPAR was 4/9 in Bela+MPA, 0/8 in Bela+low dose Tac and 2/10 in Tac+MPA, P= 0.087. The Bela+low-dose Tac regimen was associated with +8.8 mL/min/1.73 m2 increase in eGFR compared to -0.38 mL/min/1.73 m2 in Tac+MPA, P= 0.243. One graft loss occurred in the Bela+MPA group. Immunophenotyping of peripheral blood monocyte count (PBMC) showed that CD28+CD4+ and CD28+CD8+ T cells were higher in Bela+MPA patients with acute rejection compared to patients without rejection, although the difference did not reach statistical significance.

CONCLUSIONS:

Our data indicate that, in steroid free regimens, low-dose Tac maintenance is needed to prevent rejection when patients are converted to Bela, at least when the maneuver is done early after transplant.
Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: A Randomized Clinical Trial
  • Bredewold OW
  • Chan J
  • Svensson M
  • Bruchfeld A
  • de Fijter JW
  • et al.
Kidney Med. 2022 Nov 18;5(1):100574 doi: 10.1016/j.xkme.2022.100574.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This multicentre RCT randomised stable kidney transplant recipients to continue their CNI, or to switch to belatacept, for 12 months. Primary outcome was 7-year risk calculation for major cardiac events, using a score validated in kidney transplant recipients. No difference was found in the primary outcome between groups, although blood pressure was improved in the belatacept treated patients. 4 belatacept patients experienced rejection, with one graft loss. Methodology appears reasonable although no method of randomisation is reported and the study is open-label due to the different administration method for the two drugs. ITT analysis is used. The findings are perhaps not too surprising, as most of the components of the risk score (a surrogate for major cardiac events) are unlikely to be modified by a switch to belatacept, particularly given that the majority of participants were already on low-trough tacrolimus dosing. In reality, to see a significant difference in even predicted cardiovascular risk would require a longer treatment duration than the 12 months reported here.
Study Details
Aims: The aim of this study was to compare cardiovascular (CV) risk between belatacept versus calcineurin inhibitor (CNI)–based regimens in kidney transplant recipients (KTRs).
Interventions: Participants were randomly assigned to either continue with their CNI-based regimen or switch to belatacept for 12 months.
Participants: 105 kidney transplant recipients aged 18-80 years.
Outcomes: The primary outcome was the estimated CV risk. Secondary outcomes included arterial stiffness, patient survival, graft loss, traditional CVD risk factors in KTRs, acute rejection and CV events.
Follow Up: 12 months
RATIONALE & OBJECTIVE:

In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.

STUDY DESIGN:

Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.

SETTING & PARTICIPANTS:

KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.

INTERVENTION:

Continuation with a CNI-based regimen or switch to belatacept for 12 months.

OUTCOMES:

Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.

RESULTS:

Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.

LIMITATIONS:

The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year.

CONCLUSIONS:

We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.

FUNDING:

The trial has received a financial grant from Bristol-Myers Squibb.

TRIAL REGISTRATION:

EudraCT no. 2013-001178-20.
Liver
Postoperative negative-pressure incision therapy after liver transplant (PONILITRANS study): A randomized controlled trial
  • Lopez-Lopez V
  • Hiciano-Guillermo A
  • Martinez-Alarcon L
  • Delegido A
  • Alconchel F
  • et al.
Surgery. 2023 Apr;173(4):1072-1078 doi: 10.1016/j.surg.2022.11.011.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This unblinded RCT investigates the efficacy of prophylactic negative pressure incision therapy (iNPWT) in patients undergoing liver transplantation. iNPWT has been extensively studied in various surgical patient groups, where a benefit has been demonstrated but debate still exists about specific indications. This study found no significant difference in the primary outcome of surgical site infections (SSI) between the two groups. The two groups were generally homogenous but there was a higher rate of corticosteroid use in the treatment group. This could have masked a potential benefit of iNPWT but it also highlights that patient and treatment factors are stronger determinants of the risk of SSI than the wound dressing used. Further study is unlikely to contribute more to this question and should only be directed to certain high-risk patient sub-groups.
Study Details
Aims: This study aimed to compare the prophylactic use of incisional negative pressure wound therapy (iNPWT) versus the traditional use of dressings in patients undergoing liver transplantation.
Interventions: Participants were randomised to receive either iNPWT or standard surgical dressing on the closed surgical incision after liver transplant.
Participants: 120 patients undergoing elective liver transplantation.
Outcomes: The primary outcome was the incidence of surgical site infection 30 days postoperation. The secondary endpoints were surgical site events (such as surgical site infection, hematoma, dehiscence and seroma) and wound-related quality of life.
Follow Up: 30 days
BACKGROUND:

Postoperative complications of surgical incisions are frequent in liver transplantation. However, evidence justifying the use of incisional negative pressure wound therapy to improve surgical wound outcomes remains limited.

METHODS:

Participating patients were randomly assigned to receive incisional negative pressure wound therapy or standard surgical dressing on the closed surgical incision of the liver transplantation. The primary endpoint was surgical site infection incidence 30 days postoperatively. The secondary endpoints included surgical site events (ie, surgical site infection, dehiscence, hematoma, and seroma) and wound quality of life.

RESULTS:

Between December 2018 and September 2021, 108 patients (54 in the incisional negative pressure wound therapy group and 54 in the control group) were enrolled in this study. The incidence of surgical site infection at 30 days postoperatively was 7.4% in the treatment group and 13% in the control group (P = .34). The rate of surgical site events was similar in the treatment in the and control group (27.8% vs 29.6%, P = .83). In relation to wound quality of life, the mean score was 75.20 ± 7.27 in the incisional negative pressure wound therapy group and 72.82 ± 10.57 in the control group (P = .23).

CONCLUSION:

The prophylactic use of negative pressure wound therapy on primarily closed incisions did not significantly reduce incisional surgical site infection and surgical site event rates after liver transplantation compared with standard surgical dressings.
Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis
  • Aceto P
  • Punzo G
  • Di Franco V
  • Teofili L
  • Gaspari R
  • et al.
Eur J Anaesthesiol. 2023 Jan 1;40(1):39-53 doi: 10.1097/EJA.0000000000001780.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences
Conclusion: Viscoelastic tests (VETs) have been shown to have superior diagnostic ability than conventional coagulation tests (CCT) such as INR and platelet count and have become widely adopted in the intra- and perioperative management of critically ill surgical patients. Whether that diagnostic superiority translates to more efficient administration of blood products in patients undergoing liver transplantation is less clear. This systematic review analysed data from observational and randomised controlled studies to answer this question. The authors suggest that there is overall a reduced rate of transfusion of red blood cells and fresh frozen plasma, and increased use of cryoprecipitate in the VET-guided group. Rates of platelet transfusion and secondary endpoints of mortality and length of hospital stay were not different between the VET and CCT groups. Only two of the 17 studies included in the meta-analysis were RCTs. Both of these failed to demonstrate a significant difference in outcomes but were of relatively small sample sizes. The observational data, although heterogenous and generally of low to moderate quality, did consistently report a benefit to VET-guided strategies. The authors also quoted good quality studies in other surgical groups (e.g. cardiac surgery). Taken together, these findings support the growing utilisation of VETs in patients undergoing liver transplantation, but the authors recommend larger RCTs to strengthen the evidence base and further clarify the effect on clinical outcomes.
Study Details
Aims: This study aimed to compare the effectiveness of coagulation management guided by viscoelastic tests (VETs) versus conventional coagulation tests (CCTs) for reducing blood product transfusion in patients undergoing liver transplantation.
Interventions: Databases including the Cochrane Central Library, Embase, PubMed/MEDLINE, and the Transfusion Evidence Library were searched. Study eligibility was determined by two independent reviewers. Data were extracted in duplicate. Risk of bias was assessed using the Newcastle–Ottawa scale for cohort studies and the Cochrane risk-of-bias tool for randomised controlled trials.
Participants: 17 studies were included in the review.
Outcomes: The primary outcome of this study was the mean number of transfused units for each blood product, which included red blood cells (RBCs), platelets (PLTs), fresh frozen plasma, (FFP) and cryoprecipitate. The secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS).
Follow Up: N/A
BACKGROUND:

Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation.

OBJECTIVES:

To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation.

DESIGN:

Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO: CRD42021230213).

DATA SOURCES:

The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30 th January 2022.

ELIGIBILITY CRITERIA:

Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS).

RESULTS:

Seventeen studies ( n  = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P  < 0.001, I2  = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P  =  < 0.001; I2  = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P  = 0.005; I2  = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS.

CONCLUSION:

Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.
The role of graft to recipient weight ratio on enhanced recovery of the recipient after living donor liver transplantation - A systematic review of the literature and expert panel recommendations
  • Patel MS
  • Egawa H
  • Kwon YK
  • Chok KSH
  • Spiro M
  • et al.
Clin Transplant. 2022 Oct;36(10):e14630 doi: 10.1111/ctr.14630.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences
Conclusion: This systematic review was based on a broad search of multiple databases but there is no explicit reference to searching duplicate or duplicate extraction of data. 20 studies were included, with all being retrospective, observational studies. The included studies were heterogenous, with most not reporting outcomes of interest (ICU stay, hospital stay, graft function). The authors concluded that the level of evidence was low, however they make a strong recommendation that Graft-Recipient Weight Ratio >0.8% is strongly associated with enhanced recovery following liver donor liver transplantation. There is no meta-analysis conducted and only 2 of the included studies performed a statistical analysis showing a significant reduction in Small For Size Syndrome comparing GRWR >0.8% to <0.8%. The conclusion is therefore largely based upon expert consensus.
Study Details
Aims: This study aimed to determine the lower limit of graft-to-recipient weight ratio (GRWR) compatible with enhanced recovery following living donor liver transplant (LDLT) and to provide expert panel recommendations.
Interventions: Electronic databases including Ovid MEDLINE, Scopus, Embase, Google Scholar and Cochrane Central were searched. Titles and abstracts were screened by two independent reviewers. Quality of studies and recommendations grading was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Participants: 20 studies were included in the review.
Outcomes: The primary outcomes were graft function, other complications, and length of stay at hospital and intensive care unit (ICU). Secondary outcomes were patient and graft survival.
Follow Up: N/A
BACKGROUND:

There continues to be debate about the lower limit of graft-to-recipient weight ratio (GRWR) for living donor liver transplant (LDLT).

OBJECTIVES:

To identify the lower limit of GRWR compatible with enhanced recovery after living donor liver transplant and to provide international expert panel recommendations.

DATA SOURCES:

Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.

METHODS:

Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies assessing how GRWR affects recipient outcomes such as small for size syndrome, other complications, patient and graft survival, and length of stay were included.

PROTOCOL REGISTRATION:

CRD42021260794.

RESULTS:

Twenty articles were included in the qualitative synthesis, and all were retrospective observational studies. There was heterogeneity in the definition of study cohorts and key outcome measures such as small-for-size syndrome. Most studies lacked risk adjustment given limited single-center sample size. GRWR of ≥ .8% is associated with enhanced recovery. Recipients of grafts with GRWR < .8%, however, were found to have similar outcomes as those with ≥ .8% when appropriate consideration is made for portal flow modulation and recipient illness severity.

CONCLUSIONS:

GRWR ≥ .8% is often compatible with enhanced recovery, but grafts < .8% can be used in selected LDLT recipients with optimal donor-recipient selection, surgical technique, and perioperative management (Quality of Evidence; Low | Grade of Recommendation; Strong).
Does machine perfusion improve immediate and short-term outcomes by enhancing graft function and recipient recovery after liver transplantation? A systematic review of the literature, meta-analysis and expert panel recommendations
  • Ramírez-Del Val A
  • Guarrera J
  • Porte RJ
  • Selzner M
  • Spiro M
  • et al.
Clin Transplant. 2022 Oct;36(10):e14638 doi: 10.1111/ctr.14638.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences
Conclusion: In this systematic review and meta-analysis, a total of 38 studies were included in the qualitative synthesis, of those a further 28 were included in the meta-analysis. Only studies of adult deceased donor transplants were included, paediatric, split-liver or live donor related studies were excluded. The included studies compared either hypothermic machine preservation (HMP) +/- oxygenation (HOPE), normothermic machine preservation (NMP) or normothermic regional perfusion (NRP) with SCS. The focus of the study is on outcomes relating to enhanced recovery after transplantation. Overall HMP/HOPE was associated with: lower likelihood of early allograft dysfunction (EAD), decreased incidence of postreperfusion syndrome (PRS), length of hospital stay (LOS) and lower peak transaminases. No difference was found in primary nonfunction (PNF), need for renal replacement therapy (RRT) or length of ITU stay. A subgroup analysis between type of graft (DBD vs DCD) was performed and found for DCD grafts there was a higher degree of effect on reduction of EAD and PRS. The use on HMP is strongly recommended by the panel with moderate quality evidence for PRS and high quality for EAD, the greatest advantage being in DCD grafts. Overall NMP was associated with: decreased incidence of PRS, less EAD, shorter ITU stay and hospital stay as well as lower peak transaminases. No difference in PNF, need for RRT or frequency of major complications. A subgroup analysis of DBD vs DCD could not be performed. The use of NMP is strongly recommended by the panel with a moderate quality evidence in all domains apart from LOS which is low quality. Overall NRP was associated with less EAD and PNF, but compared to DBD livers there was a higher PNF rate. The use of NRP also is strongly recommended by the panel, but with a low quality evidence. The investigators performed a thorough literature search with appropriate terms and inclusion criteria, they screened 1840 articles to find their included studies. For hypothermic preservation they included mostly HOPE studies (11) and one HMP study, which are different interventions and should not be included together. For both HOPE and NMP, there is sufficient volume of evidence to support the recommendations made. For NRP was no RCT evidence considered, and only 2 prospective studies totalling 30 cases of NRP. Most of the patients included in meta-analysis (545) were from a single retrospective registry analysis, suggesting that more prospective or randomised studies with appropriate endpoints are required for NRP to be considered a beneficial intervention for the purposes of enhanced recovery.
Study Details
Aims: This study aimed to examine the role of machine perfusion on immediate and short-term outcomes following liver transplantation.
Interventions: A literature search was conducted using the following databases: Ovid MEDLINE, Embase, Google Scholar, Scopus, and Cochrane Central. Studies were selected for inclusion by two independent reviewers. The quality of studies and recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Participants: 38 studies were included in the review.
Outcomes: Primary nonfunction, postreperfusion syndrome (PRS), early allograft dysfunction, need for postoperative renal replacement therapy (RRT), length of intensive care unit (ICU) stay, length of hospital stay, biochemical parameters and early complications.
Follow Up: N/A
BACKGROUND:

Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain.

OBJECTIVES:

To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations.

DATA SOURCES:

Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.

METHODS:

Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS.

CONCLUSIONS:

The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong).
Are short-term complications associated with poor allograft and patient survival after liver transplantation? A systematic review of the literature and expert panel recommendations
  • Alconchel F
  • Tinguely P
  • Frola C
  • Spiro M
  • Ciria R
  • et al.
Clin Transplant. 2022 Oct;36(10):e14704 doi: 10.1111/ctr.14704.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review identified a total of 32 articles exploring the association between short-term complications and graft and patient survival following liver transplantation. All included studies were observational, 18 comparative and 14 non-comparative. The studies assessed found AKI, biliary complications, and early allograft disfunction (EAD) have significant effect on graft and patient survival. There was a moderate quality of evidence based on the majority of included studies that both graft and patient survival was lower when AKI, EAD and biliary complications were present, with the recommendation that efforts should be made to reduce these to improve outcomes. They found a low quality of evidence, from only 4 of the included studies that EAD was associated with AKI, CKD, donor age, donor BMI, DCD donor, steatosis, and WIT. A moderate quality of evidence from 12 studies associating biliary complications with cholestatic liver disease, roux-en-y anastomosis, low portal vein flow, high-grade portal vein thrombosis, presence of stent or t-tube and raised donor risk index. They also found a moderate quality of evidence from 7 studies associating AKI with raised BMI, prolonged IVC clamping, long CIT and massive transfusion (>10 units). The authors recommend that patients with any of the risk factors associated with key complications (AKI, EAD and biliary complications) should be considered pre-operatively and monitored closely. The authors present a comprehensive systematic review of the relevant literature, while all observational studies, there is a high volume of patients within these studies >25,000 patients. The key outcomes of graft and patient survival are present in nearly all studies. The evidence included is of sufficient quality to associate the short-term complications of AKI, EAD and biliary compilations with reduced graft and patient survival as they intended. As such, the recommendations to take steps to reduce these is a sensible one, however, the evidence of associated risk factors is of lower quality and thus it is difficult for a clinician to know clearly what factors to be weary of. A meta-analysis could have been of value but given the lack of randomised studies included to level of evidence would have remained the same. Overall, the studies highlight the key complications that could result in poorer outcomes and some risk factors associated with these complications.
Study Details
Aims: This study aimed to investigate the impact of short-term complications on patient and graft survival following liver transplantation.
Interventions: A literature search was conducted on Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Studies were selected by two independent reviewers. The quality of evidence and strength of recommendations were rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Participants: 32 studies were included in the review.
Outcomes: The outcomes of interest included patient survival, graft survival, posttransplant complications, and short-term outcomes including morbidity, mortality, length of intestive care unit (ICU) or hospital stay.
Follow Up: N/A
BACKGROUND:

Maximizing patient and allograft survival after liver transplant (LT) is important from both a patient care and organ utilization perspective. Although individual studies have addressed the effects of short-term post-LT complications on a limited scale, there has not been a systematic review of the literature formally assessing the potential effects of early complications on long-term outcomes.

OBJECTIVES:

To identify whether short-term complications after LT affect allograft and overall survival, to identify short-term complications of particular clinical interest and significance, and to provide recommendations to improve post-LT graft and patient survival.

DATA SOURCES:

Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.

METHODS:

A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel.

RESULTS:

The literature review and analysis provided show that short-term complications have a large impact on allograft and patient survival after LT. The complications with the strongest effect on survival are acute kidney injury (AKI), biliary complications, and early allograft dysfunction (EAD).

CONCLUSION:

This panel recommends taking measures to reduce the risk and incidence of short-term complications post-LT. Clinicians should pay particular attention to preventing or ameliorating AKI, biliary complications, and EAD (Quality of evidence; Moderate | Grade of Recommendation; Strong).
Other
Influence of Dexmedetomidine on Myocardial Injury in Patients with Simultaneous Pancreas-Kidney Transplantation
  • Dong A
  • Zhang Y
  • Lu S
  • Yu W
Evid Based Complement Alternat Med. 2022 Nov 17;2022:7196449 doi: 10.1155/2022/7196449.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences
Conclusion: In this RCT, patients undergoing simultaneous kidney pancreas transplant were randomised to receive an infusion of dexmedetomidine or saline. Patients were blinded to their group allocation. There were no significant differences in haemodynamic measures intra-operatively. TNF-alpha and IL-6 in the serum was significantly higher in the control group than the study group from 30 minutes into surgery until 24 hours after. Immediately after surgery cardiac troponin was significantly higher in the control group than the study group. The rise in CK-MB in both groups also fell away quicker in the study group after surgery. There was no statistically significant difference in intra-operative cardiac events or ECG changes. The study shows an ischaemia- reperfusion event after pancreas and kidney reperfusion, with possible cardiac effects. There is no power calculation and it is not clear what the primary outcome was, so the study may be underpowered.
Study Details
Aims: This study aimed to investigate the effect of dexmedetomidine (Dex) on myocardial injury in simultaneous pancreas-kidney transplant recipients.
Interventions: Participants were randomised to either the dexmedetomidine (Dex) group or the saline (control) group.
Participants: 94 simultaneous pancreas-kidney transplant recipients.
Outcomes: The outcomes of interest were changes in group haemodynamic variables, differences in inflammatory factors and myocardial injury biomarkers between the Dex and the control group, and intraoperative adverse cardiovascular events.
Follow Up: 1 year
BACKGROUND:

Diabetes is one of the most common chronic diseases in the world. End-stage renal disease (ESRD) caused by diabetes is the most serious long-term complication. The main cause of death in patients with simultaneous pancreas-kidney transplantation (SPKT) is cardiovascular disease. Although dexmedetomidine (Dex) has unique advantages in heart protection against ischaemic/reperfusion injury, few clinical studies have been conducted on its cardioprotective effect in SPKT. This study aimed to explore the influence of Dex on myocardial injury in patients undergoing SPKT and to analyze its possible mechanism.

METHODS:

A randomized controlled trial (RCT) was performed from July 1, 2018 to December 1, 2020. Eighty patients, regardless of gender, scheduled for SPKT were randomly allocated into a Dex group (D group) receiving Dex at a rate of 1 µg/kg for 10 minutes before anaesthesia induction and then continuous infusion at 0.5 µg/kg/hour until the end of surgery and control group (C group) receiving equivalent capacity of saline. Serum cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were recorded at 5 minutes after anaesthesia induction (baseline,T0), 5 minutes before renal arteriovenous opening (T1), 30 minutes after renal arteriovenous opening (T2), 30 minutes after pancreatic related arteriovenous opening (T3), immediately after surgery (T4), 4 hours after surgery (T5), and 24 hours after surgery (T6). Adverse cardiovascular events were recorded during the perioperative period. Changes in ECG S-T segments and T waves were monitored at T0-T6. Myocardial infarction and percutaneous coronary intervention were recorded with an average follow-up of one year.

RESULTS:

Compared with T0, TNF-α and IL-6 concentrations significantly increased at T1-T6 in the C and D groups (P < 0.05). IL-6 concentration increased significantly after renal artery opening and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, TNF-α, and IL-6 concentrations were significantly reduced in group D at T2-T6 (P < 0.05). Compared with T0, cTnI and CK-MB concentrations were significantly increased at T3-T6 in the C and D groups (P < 0.05). cTnI and CK-MB concentrations increased significantly after the opening of renal artery, and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, cTnI and CK-MB concentrations were significantly reduced in the D group at T3-T6 (P < 0.05). There was no significant difference in patient characteristics amongst groups, including the proportion of intraoperative vasoactive drug use and adverse cardiovascular events during the follow-up period. Heart rate, mean blood pressure, central venous pressure, and cardiac output were not remarkably different between the two groups at any time point.

CONCLUSIONS:

Perioperative reperfusion could aggravate myocardial injury in SPKT. Dex may be considered a way to reduce myocardial injury caused by inflammatory action by decreasing the release of inflammatory factors. Trial Registration Number: Chinese Clinical Trial Registry ID: ChiCTR2200060084.
Spk
Influence of Dexmedetomidine on Myocardial Injury in Patients with Simultaneous Pancreas-Kidney Transplantation
  • Dong A
  • Zhang Y
  • Lu S
  • Yu W
Evid Based Complement Alternat Med. 2022 Nov 17;2022:7196449 doi: 10.1155/2022/7196449.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences
Conclusion: In this RCT, patients undergoing simultaneous kidney pancreas transplant were randomised to receive an infusion of dexmedetomidine or saline. Patients were blinded to their group allocation. There were no significant differences in haemodynamic measures intra-operatively. TNF-alpha and IL-6 in the serum was significantly higher in the control group than the study group from 30 minutes into surgery until 24 hours after. Immediately after surgery cardiac troponin was significantly higher in the control group than the study group. The rise in CK-MB in both groups also fell away quicker in the study group after surgery. There was no statistically significant difference in intra-operative cardiac events or ECG changes. The study shows an ischaemia- reperfusion event after pancreas and kidney reperfusion, with possible cardiac effects. There is no power calculation and it is not clear what the primary outcome was, so the study may be underpowered.
Study Details
Aims: This study aimed to investigate the effect of dexmedetomidine (Dex) on myocardial injury in simultaneous pancreas-kidney transplant recipients.
Interventions: Participants were randomised to either the dexmedetomidine (Dex) group or the saline (control) group.
Participants: 94 simultaneous pancreas-kidney transplant recipients.
Outcomes: The outcomes of interest were changes in group haemodynamic variables, differences in inflammatory factors and myocardial injury biomarkers between the Dex and the control group, and intraoperative adverse cardiovascular events.
Follow Up: 1 year
BACKGROUND:

Diabetes is one of the most common chronic diseases in the world. End-stage renal disease (ESRD) caused by diabetes is the most serious long-term complication. The main cause of death in patients with simultaneous pancreas-kidney transplantation (SPKT) is cardiovascular disease. Although dexmedetomidine (Dex) has unique advantages in heart protection against ischaemic/reperfusion injury, few clinical studies have been conducted on its cardioprotective effect in SPKT. This study aimed to explore the influence of Dex on myocardial injury in patients undergoing SPKT and to analyze its possible mechanism.

METHODS:

A randomized controlled trial (RCT) was performed from July 1, 2018 to December 1, 2020. Eighty patients, regardless of gender, scheduled for SPKT were randomly allocated into a Dex group (D group) receiving Dex at a rate of 1 µg/kg for 10 minutes before anaesthesia induction and then continuous infusion at 0.5 µg/kg/hour until the end of surgery and control group (C group) receiving equivalent capacity of saline. Serum cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were recorded at 5 minutes after anaesthesia induction (baseline,T0), 5 minutes before renal arteriovenous opening (T1), 30 minutes after renal arteriovenous opening (T2), 30 minutes after pancreatic related arteriovenous opening (T3), immediately after surgery (T4), 4 hours after surgery (T5), and 24 hours after surgery (T6). Adverse cardiovascular events were recorded during the perioperative period. Changes in ECG S-T segments and T waves were monitored at T0-T6. Myocardial infarction and percutaneous coronary intervention were recorded with an average follow-up of one year.

RESULTS:

Compared with T0, TNF-α and IL-6 concentrations significantly increased at T1-T6 in the C and D groups (P < 0.05). IL-6 concentration increased significantly after renal artery opening and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, TNF-α, and IL-6 concentrations were significantly reduced in group D at T2-T6 (P < 0.05). Compared with T0, cTnI and CK-MB concentrations were significantly increased at T3-T6 in the C and D groups (P < 0.05). cTnI and CK-MB concentrations increased significantly after the opening of renal artery, and reached the peak after the opening of pancreatic blood vessels. Compared with the C group, cTnI and CK-MB concentrations were significantly reduced in the D group at T3-T6 (P < 0.05). There was no significant difference in patient characteristics amongst groups, including the proportion of intraoperative vasoactive drug use and adverse cardiovascular events during the follow-up period. Heart rate, mean blood pressure, central venous pressure, and cardiac output were not remarkably different between the two groups at any time point.

CONCLUSIONS:

Perioperative reperfusion could aggravate myocardial injury in SPKT. Dex may be considered a way to reduce myocardial injury caused by inflammatory action by decreasing the release of inflammatory factors. Trial Registration Number: Chinese Clinical Trial Registry ID: ChiCTR2200060084.