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  • Collins MG
  • Fahim MA
  • Pascoe EM
  • Hawley CM
  • Johnson DW
  • et al.
Lancet. 2023 Jul 8;402(10396):105-117 doi: 10.1016/S0140-6736(23)00642-6.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This large, multi-centre, double-blinded, randomised control trial found a reduction in DGF rate with the use of balanced crystalloid (30%) compared with normal saline (40%), a RR of 0.74 (p<0.0001). The trial was well designed, with exceptional blinding, the Plasma-Lyte and saline were packaged in custom identical bags only identifiable by serial numbers, so all parties were blinded for the duration of the trial. The trial was conducted across 16 sites, with a representative trial cohort of deceased donor kidneys (DBD:DCD of 3:1), containing only 16 (2%) of pre-emptive recipients and 20 (2%) kidneys that received HMP as preservation, which is crucial given their primary outcome. This reduction in DGF equated to 190 fewer dialysis sessions in the balanced crystalloid group and a number needed to treat of 10 to prevent 1 case of DGF. Their hypothesised effect of the fluid on post-transplant biochemistry, with reduced chloride burden, increase bicarbonate and pH with minimal effect on potassium was demonstrated and thus reduced tubular acidosis and improve blood flow leading to lower rates of DGF is sound. The trial has few limitations, laboratory data wasn’t collected beyond post-operative day 2 and other minor data points such as blood pressure and surgical anastomosis time, however given the trial size and randomisation strategy limiting centre effect, this is likely of no consequence. It is important to note that the effect is not necessarily generalisable to other balanced crystalloids such as Hartman’s, given that contains more chloride as well as lactate and further work would be needed to assess their benefit. This trial provides robust evidence sufficient to warrant consideration of changing practice, Plasma-Lyte is readily available, relatively inexpensive and in the context of renal transplant providing likely reduction in DGF.
Aims: To assess if use of balanced crystalloid vs saline reduces rates of delayed graft function.
Interventions: The intervention group received a balanced crystalloid in the form of Plasma-Lyte 148 intra- and post-operatively for intravenous volume replacement vs standard care who received 0.9% sodium chloride.
Participants: 808 participants, adults and children receiving kidney only transplant.
Outcomes: The primary outcome was DGF, which they defined as need for dialysis within the first 7 days. Secondary outcomes included: number of dialysis treatments, duration of dialysis in days, ranked composite of DGF and day2 creatinine reduction ratio, post-op hyperkalaemia, peak potassium, fluid overload, urine output, use of inotropes, acute rejection, number of biopsies, mortality, graft survival, graft function and hospital stay.
Follow Up: 52 weeks
BACKGROUND:

Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF.

METHODS:

BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488).

FINDINGS:

Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48).

INTERPRETATION:

Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation.

FUNDING:

Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

  • Allen NC
  • Martin AJ
  • Snaidr VA
  • Eggins R
  • Chong AH
  • et al.
N Engl J Med. 2023 Mar 2;388(9):804-812 doi: 10.1056/NEJMoa2203086.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This blinded placebo-controlled RCT investigated the efficacy of nicotinamide therapy in preventing keratinocyte cancers in transplant patients on immunosuppressive therapy. 158 participants who had a background of previous keratinocyte cancer were randomised to receive nicotinamide therapy or placebo, and were followed up for one year. There was no significant difference in the rates of new cancers between the treatment and placebo groups. The study was limited by small sample size but also a lower rate of new keratinocyte cancers in both groups than what was expected based on other studies. Although participants that had taken nicotinamide up to 3 months prior were excluded, data on longer term use in the past was not collected. Given that nicotinamide prescription amongst transplant physicians is common, it is possible that many of the participants had previously been on long-term nicotinamide therapy. This could account for the comparatively low rate of new cancers in both groups, and is a major confounding factor of the reported outcomes.
Aims: The aim of this study was to determine the role of oral nicotinamide in skin-cancer chemoprevention in organ transplant patients.
Interventions: Participants were randomised to receive either nicotinamide or placebo.
Participants: 158 organ-transplant recipients with at least two keratinocyte cancers in the past 5 years.
Outcomes: The primary outcome was the number of new keratinocyte cancers. The secondary outcomes were the numbers of squamous-cell and basal-cell carcinomas, the number of actinic keratoses, safety, and quality of life.
Follow Up: 12 months
BACKGROUND:

Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear.

METHODS:

In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life.

RESULTS:

A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups.

CONCLUSIONS:

In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

  • Singer J
  • Tunbridge M
  • Perkins GB
  • Salehi T
  • Ying T
  • et al.
BMJ Open. 2022 Dec 1;12(12):e062747 doi: 10.1136/bmjopen-2022-062747.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This manuscript describes the protocol of an upcoming multi-centre, double blinded RCT of a size larger than many previous RCTs, attempting to assess gut biome effects on vaccine responses. Of the 26 previously conducted RCTs around 50% have demonstrated some beneficial effects of probiotics on vaccine response. It has been commented that the response may be reduced as none of these trials contained patients who had a disrupted microbiome, including immunosuppressed renal recipients. The intervention has been previously demonstrated to improve the gut biome and increase reactivity to parenteral vaccines. The authors propose a well-designed study with sound methodology, containing a clearly defined primary outcome which can be unambiguously tested. The proposed intervention is unlikely to have any serious adverse events and is inexpensive. Based on previous literature it is a study that has good potential.
Aims: This study aims to examine whether dietary fibre supplementation will lead to attenuation of gut dysbiosis and promote vaccine responsiveness in renal transplant patients.
Interventions: Patients will be randomly assigned to receive either inulin (active) or maltodextrin (placebo).
Participants: Kidney transplant recipients (age ≥ 18 years).
Outcomes: The primary endpoint is the proportion of participants to achieve in vitro neutralisation of live SARS-CoV-2 virus four weeks after the third dose of the COVID-19 vaccine. Secondary endpoints are safety and tolerability of dietary inulin, vaccine-specific immune cell populations and responses, and the diversity and differential abundance of gut microbiota.
Follow Up: 4- 6 weeks following vaccination.
INTRODUCTION:

Kidney transplant recipients (KTRs) are at an increased risk of hospitalisation and death from COVID-19. Vaccination against SARS-CoV-2 is our primary risk mitigation strategy, yet vaccine effectiveness in KTRs is suboptimal. Strategies to enhance vaccine efficacy are therefore required. Current evidence supports the role of the gut microbiota in shaping the immune response to vaccination. Gut dysbiosis is common in KTRs and is a potential contributor to impaired COVID-19 vaccine responses. We hypothesise that dietary fibre supplementation will attenuate gut dysbiosis and promote vaccine responsiveness in KTRs.

METHODS AND ANALYSIS:

Rapamycin and inulin for third-dose vaccine response stimulation-inulin is a multicentre, randomised, prospective, double-blinded, placebo-controlled pilot trial examining the effect of dietary inulin supplementation prior to a third dose of COVID-19 vaccine in KTRs who have failed to develop protective immunity following a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to inulin (active) or maltodextrin (placebo control), administered as 20 g/day of powdered supplement dissolved in water, for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm that achieve in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third dose of COVID-19 vaccine. Secondary outcomes include the safety and tolerability of dietary inulin, the diversity and differential abundance of gut microbiota, and vaccine-specific immune cell populations and responses.

ETHICS AND DISSEMINATION:

Ethics approval was obtained from the Central Adelaide Local Health Network (CALHN) Human Research Ethics Committee (HREC) (approval number: 2021/HRE00354) and the Sydney Local Health District (SHLD) HREC (approval numbers: X21-0411 and 2021/STE04280). Results of this trial will be published following peer-review and presented at scientific meetings and congresses.

TRIAL REGISTRATION NUMBER:

ACTRN12621001465842.

  • Collins MG
  • Fahim MA
  • Pascoe EM
  • Hawley CM
  • Johnson DW
  • et al.
Transplant Direct. 2022 Nov 4;8(12):e1399 doi: 10.1097/TXD.0000000000001399.
UNLABELLED:

Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail.

METHODS:

We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients.

RESULTS:

During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences.

CONCLUSIONS:

BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.

  • Tunbridge M
  • Perkins GB
  • Singer J
  • Salehi T
  • Ying T
  • et al.
Trials. 2022 Sep 15;23(1):780 doi: 10.1186/s13063-022-06634-w.
UNLABELLED:

Kidney transplant recipients are at an increased risk of severe COVID-19-associated hospitalisation and death. Vaccination has been a key public health strategy to reduce disease severity and infectivity, but the effectiveness of COVID vaccines is markedly reduced in kidney transplant recipients. Urgent strategies to enhance vaccine efficacy are needed.

METHODS:

RIVASTIM-rapamycin is a multicentre, randomised, controlled trial examining the effect of immunosuppression modification prior to a third dose of COVID-19 vaccine in kidney transplant recipients who have failed to develop protective immunity to a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to either remain on standard of care immunosuppression with tacrolimus, mycophenolate, and prednisolone (control) or cease mycophenolate and commence sirolimus (intervention) for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm who develop protective serological neutralisation of live SARS-CoV-2 virus at 4-6 weeks following a third COVID-19 vaccination. Secondary outcomes include SARS-CoV-receptor binding domain IgG, vaccine-specific immune cell populations and responses, and the safety and tolerability of sirolimus switch.

DISCUSSION:

Immunosuppression modification strategies may improve immunological vaccine response. We hypothesise that substituting the mTOR inhibitor sirolimus for mycophenolate in a triple drug regimen will enhance humoral and cell-mediated responses to COVID vaccination for kidney transplant recipients.

TRIAL REGISTRATION:

Australia New Zealand Clinical Trials Registry ACTRN12621001412820. Registered on 20 October 2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382891&isReview=true.

  • Pascoe EM
  • Chadban SJ
  • Fahim MA
  • Hawley CM
  • Johnson DW
  • et al.
Trials. 2022 Jan 18;23(1):52 doi: 10.1186/s13063-021-05989-w.
CET Conclusion
Reviewer: Centre for Evidence in Transplantation
Conclusion: Protocol statistics: no CET conclusion
Aims: This protocol for a randomised controlled trial aims to investigate the effect of intravenous fluid therapy with balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), compared to saline in the incidence of delayed graft function in among deceased donor renal transplant patients.
Interventions: Participants will be randomised to either the Plasmalyte group or the saline group.
Participants: Deceased donor kidney transplant recipients.
Outcomes: The primary endpoint is the incidence of delayed graft function. The secondary endpoints include early kidney transplant function, treatment for hyperkalaemia, and graft survival.
Follow Up: 12 months
BACKGROUND:

Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial.

METHODS AND DESIGN:

BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome.

DISCUSSION:

BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases.

TRIAL REGISTRATION:

Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019.

  • Chadban SJ
  • McDonald M
  • Wyburn K
  • Opdam H
  • Barry L
  • et al.
Kidney Int. 2020 Dec;98(6):1616-1618 doi: 10.1016/j.kint.2020.10.007.
  • Collins MG
  • Fahim MA
  • Pascoe EM
  • Dansie KB
  • Hawley CM
  • et al.
Trials. 2020 May 25;21(1):428 doi: 10.1186/s13063-020-04359-2.
BACKGROUND:

Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown.

METHODS:

BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry.

DISCUSSION:

If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide.

TRIAL REGISTRATION:

Australian New Zealand Clinical Trials Registry: ACTRN12617000358347. Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488. Registered on 4 February 2019.

  • Schinstock CA
  • Mannon RB
  • Budde K
  • Chong AS
  • Haas M
  • et al.
Transplantation. 2020 May;104(5):911-922 doi: 10.1097/TP.0000000000003095.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

  • Chadban SJ
  • Ahn C
  • Axelrod DA
  • Foster BJ
  • Kasiske BL
  • et al.
Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103 doi: 10.1097/TP.0000000000003136.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.