AIMS:

Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.

METHODS:

In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.

RESULTS:

Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.

CONCLUSION:

This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.

IMPORTANCE:

Patients with advanced chronic kidney disease (CKD) have the best chance for a longer and healthier life if they receive a kidney transplant. However, many barriers prevent patients from receiving a transplant.

OBJECTIVES:

To evaluate the effect of a multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant.

DESIGN, SETTING, AND PARTICIPANTS:

This pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster randomized clinical trial included all 26 CKD programs in Ontario, Canada, from November 1, 2017, to December 31, 2021. These programs provide care for patients with advanced CKD (patients approaching the need for dialysis or receiving maintenance dialysis).

INTERVENTIONS:

Using stratified, covariate-constrained randomization, allocation of the CKD programs at a 1:1 ratio was used to compare the multicomponent intervention vs usual care for 4.2 years. The intervention had 4 main components, (1) administrative support to establish local quality improvement teams; (2) transplant educational resources; (3) an initiative for transplant recipients and living donors to share stories and experiences; and (4) program-level performance reports and oversight by administrative leaders.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor.

RESULTS:

The 26 CKD programs (13 intervention, 13 usual care) during the trial period included 20 375 potentially transplant-eligible patients with advanced CKD (intervention group [n = 9780 patients], usual-care group [n = 10 595 patients]). Despite evidence of intervention uptake, the step completion rate did not significantly differ between the intervention vs usual-care groups: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio, 1.00 (95% CI, 0.87-1.15).

CONCLUSIONS AND RELEVANCE:

This novel multicomponent intervention did not significantly increase the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT03329521.

BACKGROUND:

Living donor kidney transplantation (LDKT) is the optimal treatment for eligible patients with kidney failure, although it is underutilized. Contextually tailored patient- and family-centered interventions may be effective to increase LDKT.

OBJECTIVE:

We outline a protocol to test the feasibility of the Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT) intervention designed to increase LDKT.

DESIGN:

Non-blinded single-center pilot randomized controlled trial with a qualitative interview component.

SETTING:

Academic transplant referral center in Northern Alberta Region with a population of more than 2 million in its catchment area.

PATIENTS:

English-speaking patients of the age range 18 to 75 years who are referred for kidney transplantation are eligible to participate.

MEASUREMENTS:

Feasibility will be assessed by indicators of recruitment, retention, and completion rates, treatment fidelity, adherence to intervention, engagement in intervention, and acceptability.

METHODS:

Participants will be randomly assigned 1:1 to either standard care (control) or the experimental group who receive standard care plus the MuST AKT intervention, a person-centered program designed to assist and enable the kidney transplant candidate to achieve what is required to receive an LDKT. The intervention consists of an introductory session and 4 intervention sessions delivered in-person or virtually.

LIMITATIONS:

Inferences cannot be drawn regarding the efficacy/effectiveness of the MuST AKT intervention. This study is non-blinded.

CONCLUSIONS:

This pilot study is the first step in our broader initiative to increase LDKT in our health care jurisdiction. The results of this study will be used to inform the development of a future definitive randomized controlled trial.

TRIAL REGISTRATION NUMBER:

NCT04666545.

INTRODUCTION:

Racial/ethnic disparities in living donor kidney transplantation (LDKT) are a persistent challenge. Although nearly all directed donations are from members of patients' social networks, little is known about which social network members take steps toward living kidney donation, which do not, and what mechanisms contribute to racial/ethnic LDKT disparities.

METHODS:

We describe the design and rationale of the Friends and Family of Kidney Transplant Patients Study, a factorial experimental fielding two interventions designed to promote LKD discussions. Participants are kidney transplant candidates at two centers who are interviewed and delivered an intervention by trained center research coordinators. The search intervention advises patients on which social network members are most likely to be LKD contraindication-free; the script intervention advises patients on how to initiate effective LKD discussions. Participants are randomized into four conditions: no intervention, search only, script only, or both search and script. Patients also complete a survey and optionally provide social network member contact information so they can be surveyed directly. This study will seek to enroll 200 transplant candidates. The primary outcome is LDKT receipt. Secondary outcomes include live donor screening and medical evaluations and outcomes. Tertiary outcomes include LDKT self-efficacy, concerns, knowledge, and willingness, measured before and after the interventions.

CONCLUSION:

This study will assess the effectiveness of two interventions to promote LKD and ameliorate Black-White disparities. It will also collect unprecedented information on transplant candidates' social network members, enabling future work to address network member structural barriers to LKD.

INTRODUCTION:

In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US).

METHODS:

A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers.

RESULTS:

Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion.

CONCLUSION:

Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT.

The transplant community has faced unprecedented challenges balancing risks of performing living donor transplants during the COVID-19 pandemic with harms of temporarily suspending these procedures. Decisions regarding postponement of living donation stem from its designation as an elective procedure, this despite that the Centers for Medicare and Medicaid Services categorise transplant procedures as tier 3b (high medical urgency-do not postpone). In times of severe resource constraints, health systems may be operating under crisis or contingency standards of care. In this manuscript, the United Network for Organ Sharing Ethics Workgroup explores prioritisation of living donation where health systems operate under contingency standards of care and provide a framework with recommendations to the transplant community on how to approach living donation in these circumstances.To guide the transplant community in future decisions, this analysis suggests that: (1) living donor transplants represent an important option for individuals with end-stage liver and kidney disease and should not be suspended uniformly under contingency standards, (2) exposure risk to SARS-CoV-2 should be balanced with other risks, such as exposure risks at dialysis centres. Because many of these risks are not quantifiable, donors and recipients should be included in discussions on what constitutes acceptable risk, (3) transplant hospitals should strive to maintain a critical transplant workforce and avoid diverting expertise, which could negatively impact patient preparedness for transplant, (4) transplant hospitals should consider implementing protocols to ensure early detection of SARS-CoV-2 infections and discuss these measures with donors and recipients in a process of shared decision-making.

BACKGROUND:

Recent studies have shown that donor nephrectomy can induce renal function impairment. However, few meta-analysis studies about this have proceeded. Therefore, the objective of this systematic review and meta-analysis including all data of recent research studies was to determine whether living donor nephrectomy (LDN) could induce renal function impairment.

METHODS:

By November 2020, comprehensive literature searches were performed on PubMed, Embase, and Cochrane databases. Inclusion criteria were: (1) observational studies with data about overall end-stage renal disease (ESRD) or chronic kidney disease (CKD) of living kidney donors, (2) control group consisted of people without donor nephrectomy, and (3) outcomes of studies included long-term end-stage renal disease risks after living kidney donation. Risk of Bias in Non-randomized Studies of interventions (ROBINS-I) assessment tool was used to evaluate our methodological quality.

RESULTS:

The qualitative review included 11 studies and the meta-analysis included 5 studies. In the meta-analysis, the integrated overall ESRD risk was 5.57 (95% CI: 2.03-15.30). Regarding the overall risk of bias using ROBINS-I assessment tool, 0 studies was rated as "Low", 7 studies were rated as "moderate", 2 studies were rated as "Serious", and two studies were rated as "Critical".

CONCLUSIONS:

Our study showed that LDN increased ESRD risk in LDN patients. However, in our meta-analysis, variables in included studies were not uniform and the number of included studies was small. To have a definite conclusion, meta-analyses of well-planned and detailed studies need to be conducted in the future.

OBJECTIVE:

Living kidney donors (LKDs) experience perioperative anxiety. We designed the following study to evaluate the anxiolytic effect of transcutaneous electrical acupoint stimulation (TEAS) during the perioperative period in a group of LKDs undergoing laparotomy nephrectomy.

METHODS:

LKDs were randomly assigned to either the TEAS or control group. Participants in the TEAS group received 30min of intervention (6-15 mA, 2-100 Hz), at Yintang (EX-HN-3), bilateral Taichong (LR3) and Neiguan (PC6) one day before surgery (D0), before induction of anesthesia (D1) and one day after surgery (D2). The participants in the control group received the same placement of electrodes but without electrical stimulation. Venous blood was collected before each intervention. Anxiety levels and recovery profiles were recorded.

RESULTS:

LKDs in the TEAS group had lower anxiety level than those in the control group at D1, D2 and three days after surgery (D3). The percentage differences were: 33.3%, 25.0%, and 22.2%; [95% confidence interval (CI), (-55.1%, -11.6%), (-47.4%, -2.6%), and (-42.3%, -2.2%); P = 0.005, P = 0.034, and P = 0.035; respectively]. LKDs who received TEAS had better sleep quality and short-term recovery profiles than those in the control group. The plasma levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) in the TEAS group were significantly higher than those in the control group at D1 and D2 (5-HT: P = 0.001, and P < 0.001; MT: P = 0.006, and P = 0.001). At the 3-month follow up, fewer LKDs in the TEAS group had incisional pain when compared to the control group (P = 0.032).

CONCLUSIONS:

Perioperative TEAS decreased perioperative anxiety and facilitated postoperative recovery in the LKDs, and potential decreased the development of chronic pain. Trial Registration: Registered at ChiCTR2000029891, http://www.chictr.org.cn/listbycreater.aspx.

The objective of this study was to investigate reasons for or against anonymity that are pertinent to kidney paired donations (KPD). We conducted a systematic review of reasons using PubMed and Google Scholar until May 2022 and through snowballing. Inclusion criteria were publications that: 1) discussed organ donation anonymity; 2) was peer-reviewed; 3) presented at least one reason on anonymity. Exclusion criteria: 1) not published in a scientific journal; 2) grey literature and dissertations. Four researchers independently reviewed and selected papers based on the criteria, extracted text passages and coded them into narrow and broad reason types, selected reasons that were valid for kidney paired donations. 50 articles were included, 62 narrow reasons (n = 24 for; n = 38 against) and 13 broad reasons were coded. Broad reasons were: protection against harm, general benefits, gratitude, curiosity, unrealistic to implement, fundamental rights, respect people's wishes, professional neutrality, timing is important, information disclosure, altruism, reciprocity and donation pool. We did not find reasons that justify legal prohibition of donor-recipient interactions for KPD, if they consented to meet. Professional counselling, follow-up and careful evaluations to prevent potential harm.