AIMS:

The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT).

METHODS AND RESULTS:

In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] μg/mL vs. 1.6 [1.20-3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] μg/mL vs. 0.9 [0.45-2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups.

CONCLUSIONS:

Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.

BACKGROUND:

Patients after kidney transplantation eventually face the risk of graft loss with the concomitant need for dialysis or retransplantation. Choosing the right kidney replacement therapy after graft loss is an important preference-sensitive decision for kidney transplant recipients. However, the rate of conversations about treatment options after kidney graft loss has been shown to be as low as 13% in previous studies. It is unknown whether the implementation of artificial intelligence (AI)-based risk prediction models can increase the number of conversations about treatment options after graft loss and how this might influence the associated shared decision-making (SDM).

OBJECTIVE:

This study aims to explore the impact of AI-based risk prediction for the risk of graft loss on the frequency of conversations about the treatment options after graft loss, as well as the associated SDM process.

METHODS:

This is a 2-year, prospective, randomized, 2-armed, parallel-group, single-center trial in a German kidney transplant center. All patients will receive the same routine post-kidney transplant care that usually includes follow-up visits every 3 months at the kidney transplant center. For patients in the intervention arm, physicians will be assisted by a validated and previously published AI-based risk prediction system that estimates the risk for graft loss in the next year, starting from 3 months after randomization until 24 months after randomization. The study population will consist of 122 kidney transplant recipients >12 months after transplantation, who are at least 18 years of age, are able to communicate in German, and have an estimated glomerular filtration rate <30 mL/min/1.73 m2. Patients with multi-organ transplantation, or who are not able to communicate in German, as well as underage patients, cannot participate. For the primary end point, the proportion of patients who have had a conversation about their treatment options after graft loss is compared at 12 months after randomization. Additionally, 2 different assessment tools for SDM, the CollaboRATE mean score and the Control Preference Scale, are compared between the 2 groups at 12 months and 24 months after randomization. Furthermore, recordings of patient-physician conversations, as well as semistructured interviews with patients, support persons, and physicians, are performed to support the quantitative results.

RESULTS:

The enrollment for the study is ongoing. The first results are expected to be submitted for publication in 2025.

CONCLUSIONS:

This is the first study to examine the influence of AI-based risk prediction on physician-patient interaction in the context of kidney transplantation. We use a mixed methods approach by combining a randomized design with a simple quantitative end point (frequency of conversations), different quantitative measurements for SDM, and several qualitative research methods (eg, records of physician-patient conversations and semistructured interviews) to examine the implementation of AI-based risk prediction in the clinic.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT06056518; https://clinicaltrials.gov/study/NCT06056518.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):

PRR1-10.2196/54857.

PURPOSE:

The choice between using the internal or external iliac arteries to supply a transplanted kidney poses a dilemma during renal transplantation. As the internal iliac artery branches to the genital tract, cutting it could potentially result in sexual dysfunction. The purpose of this study was to compare the effects of these two surgical methods on sexual function.

MATERIALS AND METHODS:

122 sexually active male patients under the age of sixty were randomly divided into two groups: the internal iliac anastomosis group and the external iliac artery anastomosis group. Before surgery and one year after the procedure, patients completed the International Index of Erectile Function-15 questionnaire (IIEF- 15), and the difference in scores of each domain was measured.

RESULTS:

Statistically, kidney transplantation improved all domains of IIEF in both groups, except for erectile function in patients who underwent internal iliac artery anastomosis group. Additionally, there were significant differences between the two groups in the domains of erectile function (p-value=0.04) and overall satisfaction (p-value = 0.002), while other domains such as orgasmic function, sexual desire, and intercourse satisfaction did not show any statistically significant differences.

CONCLUSION:

In conclusion, the choice between using the internal or external iliac artery for arterial anastomosis during kidney transplantation does not significantly impact graft function. However, it may negatively affect erectile function in patients who undergo internal iliac artery anastomosis.

BACKGROUND:

Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.

METHODS:

The INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.

DISCUSSION:

No effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT04561986. Registered on September 24, 2020.

BACKGROUND:

The aim of this open-label, multicenter, randomized controlled study was to investigate whether the life cycle pharma (LCP)-tacrolimus compared with the extended-release (ER)-tacrolimus formulation results in a difference in the prevalence of posttransplant diabetes, hypertension and chronic kidney disease (CKD) at 12 mo after liver transplantation.

METHODS:

Patients were 1:1 randomized to either of the 2 tacrolimus formulations. The primary endpoint was defined as a composite endpoint of any of 3 events: sustained (>3 mo postrandomization) posttransplant diabetes, new-onset hypertension, and/or CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 for >3 m during the follow-up.

RESULTS:

In total, 105 patients were included. In the intention-to-treat analysis, a statistically significant lower proportion of liver transplant recipients in the LCP-tacrolimus group reached the composite primary endpoint at 12 mo compared with the ER-tacrolimus group (50.9% [27/53], 95% confidence interval [CI], 37.9%-63.9% versus 71.2% [37/52], 95% CI, 57.7%-81.7%; risk difference: 0.202; 95% CI, 0.002-0.382; P = 0.046). No significant difference was found in the per protocol analysis. In the intention-to-treat and per protocol population, fewer liver transplant recipients in the LCP-tacrolimus group developed CKD and new-onset hypertension compared with the ER-tacrolimus group. No differences in rejection rate, graft and patient survival were found.

CONCLUSIONS:

A statistically significant and clinically relevant reduction in the prevalence of the composite primary endpoint was found in the LCP-tacrolimus group compared with the ER-tacrolimus group in the first year after liver transplantation with comparable efficacy.

INTRODUCTION:

Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28.

METHODS AND ANALYSIS:

We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.

ETHICS AND DISSEMINATION:

The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.

TRIAL REGISTRATION NUMBER:

NCT05664204.

OBJECTIVES:

To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients.

METHODS:

In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort.

RESULTS:

Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040).

CONCLUSIONS:

MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.