Representation of Women in Contemporary Kidney Transplant Trials.

Women are often underrepresented in clinical trials. It is unclear if this applies to trials in kidney transplant (KT) and whether the intervention or trial focus influences this. In this study, the weighted participation-to-prevalence ratio (PPR) for women enrollees in KT trials was determined for leading medical transplant or kidney journals between 2018 and 2023 using meta-regression overall and in three sensitivity analyses by: 1) Whether the intervention involved immunosuppression; 2) Area of trial focus; rejection, cardiometabolic, infection, lifestyle, surgical; 3) Whether the intervention was medical/surgical or social/behavioral. Overall, 33.7% of participants in 24 trials were women. The overall pooled PPR for the included trials was 0.80, 95% CI 0.76-0.85, with significant heterogeneity between trials (I 2 56.6%, p-value < 0.001). Women had a lower PPR when the trial involved immunosuppression (PPR 0.77, 95% CI 0.72-0.82) than when it did not (PPR 0.86, 95% CI 0.80-0.94) and were less likely to participate in trials with a medical/surgical versus behavioral intervention; the lowest PPR for women was in studies examining rejection risk (PPR 0.75, 95% CI 0.70-0.81). There is better representation of women in KT trials compared to other medical disciplines, however women remain underrepresented in transplant trials examining immunosuppression and rejection.

Disparities in Deceased Donor Kidney Offer Acceptance: A Survey of Canadian Transplant Nephrologists, General Surgeons and Urologists.

Background: Significant variability in organ acceptance thresholds have been demonstrated across the United States, but data regarding the rate and rationale for kidney donor organ decline in Canada are lacking. Objective: To examine decision making regarding deceased kidney donor acceptance and non-acceptance in a population of Canadian transplant professionals. Design: A survey study of theoretical deceased donor kidney cases of increasing complexity. Setting: Canadian transplant nephrologists, urologists, and surgeons making donor call decisions responding to an electronic survey between July 22 and October 4, 2022. Participants: Invitations to participate were distributed to 179 Canadian transplant nephrologists, surgeons, and urologists through e-mail. Participants were identified by contacting each transplant program and requesting a list of physicians who take donor call. Measurements: Survey respondents were asked whether they would accept or decline a given donor, assuming there was a suitable recipient. They were also asked to cite reasons for donor non-acceptance. Methods: Donor scenario-specific acceptance rates (total acceptance divided by total number of respondents for a given scenario and overall) and reasons for decline were determined and presented as a percentage of the total cases declined. Results: In all, 72 respondents from 7 provinces completed at least one question of the survey, with considerable variability between acceptance rates for centers; the most conservative center declined 60.9% of donor cases, whereas the most aggressive center declined only 28.1%, P-value < .001. There was an increased risk of non-acceptance with advancing age, donation after cardiac death, acute kidney injury, chronic kidney disease, and comorbidities. Limitations: As with any survey, there is the potential for participation bias. In addition, this study examines donor characteristics in isolation, however, asks respondent to assume there is a suitable candidate available. In reality, whenever donor quality is considered, it should be considered in the context of the intended recipient. Conclusion: In a survey of increasingly medically complex deceased kidney donor cases, there was significant variability in donor decline among Canadian transplant specialists. Given relatively high rates of donor decline and apparent heterogeneity in acceptance decisions, Canadian transplant specialists may benefit from additional education regarding the benefits achieved from even medically complex kidney donors for appropriate candidates relative to remaining on dialysis on the transplant waitlist.

Contexte: Une importante variabilité a été observée aux États-Unis dans le seuil d'acceptation des organes. Au Canada, on manque de données sur le taux de refus des donneurs de reins et sur les raisons qui expliquent ce refus. Objectifs: Examiner la prise de décision quant à l'acceptation ou non d'un donneur de rein décédé dans une population de professionnels de la transplantation canadiens. Conception: Un sondage exposant des cas théoriques de plus en plus complexes de donneurs de reins décédés. Cadre: Des néphrologues, urologues et chirurgiens canadiens spécialisés en transplantation qui prennent des décisions relatives au don d'organes ont été invités à répondre à un sondage électronique entre le 22 juillet et le 4 octobre 2022. Participants: L'invitation à participer a été distribuée par courriel à 179 néphrologues, chirurgiens et urologues canadiens spécialisés en transplantation. Les participants ont été identifiés en communiquant avec chaque program de transplantation pour obtenir une liste des médecins recevant des offres d'organes. Mesures: Les répondants devaient indiquer s'ils accepteraient ou refuseraient un donneur donné, en supposant qu'un receveur approprié existait. Ils étaient également invités à citer les raisons justifiant le refus d'un donneur. Méthodologie: Les taux d'acceptation par scénario (acceptation totale divisée par le nombre total de répondants pour un scénario donné, et pour l'ensemble) et les raisons du refus ont été déterminés et présentés sous forme de pourcentage du nombre total de cas refusés. Résultats: En tout, 72 professionnels issus de 7 provinces avaient répondu à au moins une question du sondage. On a observé une grande variabilité du taux d'acceptation entre les différents centers; le plus conservateur avait refusé 60,9 % des donneurs présentés alors que le plus entreprenant n'avait refusé que de 28,1 % des cas (p < 0,001). Les donneurs d'âge avancé, ceux décédés d'un problème cardiaque et ceux qui souffraient d'insuffisance rénale aiguë, d'insuffisance rénale chronique et de comorbidités étaient plus susceptibles d'être refusés. Limites: Comme pour toute étude sous forme de sondage, celle-ci comporte un possible biais de participation. Cette étude examine les caractéristiques du donneur de manière isolée, mais demande aux répondants de supposer qu'un candidat approprié existe. Dans la réalité, chaque fois que la qualité d'un donneur est évaluée, elle doit être prise en compte dans le contexte du receveur visé. Conclusion: Dans cette étude présentant des cas théoriques de complexité croissante sur le plan médical de donneurs de reins décédés, une importante variabilité a été observée quant au refus des donneurs par les spécialistes de la transplantation canadiens. Les taux relativement élevés de refus et l'apparente hétérogénéité des décisions liées à l'acceptation justifient plus d'éducation auprès des spécialistes de la transplantation canadiens; notamment sur les avantages pour un candidat approprié de recevoir un organe, même si ce dernier provient d'un cas médicalement complexe, par rapport au fait de rester en dialyze sur la liste d'attente pour une transplantation.

Donor-Recipient Matching in Kidney Transplant: We're Not There Yet.

BACKGROUND: Strategic organ allocation is expected to prolong patient and graft survival after transplant. This study explored differences in graft survival when kidneys are allocated based on strategic donor-recipient (D-R) pairing vs with the existing Kidney Allocation System (KAS). METHODS: Using the Scientific Registry of Transplant Recipients from 2000 to 2014, we used a multivariable Cox model to assess the hazard ratios (HRs) for death or graft failure among 3 hypothetical donor kidneys transplanted into 3 hypothetical recipients, relative to an ideally matched D-R pair. Median predicted survival for each of the 9 possible D-R pairing combinations was determined, and outcomes for strategic D-R pairing were compared with those obtained using the KAS for allocation. RESULTS: A total of 31,607 patients (29.7%) died or developed graft loss over the study period. Strategic allocation of kidneys resulted in HRs for graft loss of 1.74 (95% confidence interval [CI], 1.41-2.14), 1.82 (95% CI, 1.46-2.26), and 1.74 (95% CI 1.38-2.19) for recipients 1, 2 and 3 respectively, whereas by following the KAS, HRs were 1.93 (95%, CI 1.63-2.28), 2.06 (95% CI, 1.74-2.44), and 1.93 (95% CI, 1.58-2.37); corresponding to 3.84, 11.39, and 7.40 months longer predicted patient or graft survival for recipients 1, 2 and 3 with strategic D-R pairing compared with the KAS. CONCLUSIONS: Allocation of kidneys by strategic D-R pairing may improve graft survival relative to allocation using the KAS.

Predictors of Need for First and Recurrent Emergency Medical Service Transport to Emergency Department after Dialysis Initiation.

Background: Dialysis patients are frequently transported to the emergency department (ED) by Emergency Medical Services (EMS) due to acute and severe illness. However, little is known about predictors of first and recurrent transport to the ED (EMS-ED), based on characteristics at the time of dialysis initiation.Methods: We analyzed a cohort of adult (≥18 years) patients affiliated with a large quaternary care center who initiated chronic dialysis from 2009 to 2013 (last follow-up: 2015). Data on patient characteristics at the time of dialysis initiation were linked to regional EMS data. Candidate predictors of first and recurrent EMS-ED transport included comorbid conditions, dialysis characteristics and frailty severity (using the first version of the clinical frailty scale score; CFS). Time to first EMS-ED was analyzed using a multivariable sub-hazards regression model accounting for competing events (transplantation or death). Time to recurrent EMS-ED was analyzed using the Anderson-Gill counting approach, accounting for competing risks.Results: A total of 455 patients were included in the study, 243 (53%) had 1+ EMS-ED events, 90 (20%) never required an EMS-ED at last follow-up, and 69 (15%) and 53 (12%) experienced transplant or death as their first event, respectively. The mean age of the cohort was 62 ± 15 years, 89% were Caucasian, and 35% were female sex. Patients were highly comorbid and 97/381 (25.5%) with available data on frailty severity had a CFS score of ≥5, inclusive of CFS scores ranging from mildly to severely frail. After adjustment, a CFS score of ≥5 (relative to 1-2) was associated with a > 2-fold increase in the risk of first EMS-ED (subdistribution relative hazard; SHR 2.28, 95% confidence interval; CI 1.30-3.98). A history of peripheral vascular disease (SHR 1.43, 95% CI 1.00-2.03) and rheumatologic disease (SHR 1.84, 95% CI 1.00-3.38) was also associated with first EMS-ED. Frailty severity was the only factor associated with recurrent EMS-ED.Conclusion: Patients are at a high risk of EMS-ED after dialysis initiation. Frailty severity (at the time of dialysis initiation) is a strong predictor of first and recurrent EMS-ED and this may be important to guide informed decision making and resource planning for dialysis patients who require EMS.

Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later?

Currently many but not all centers transplant hepatitis C virus (HCV) viremic positive (+) donor kidneys into HCV+ recipients. Directed donation of HCV+ organs reduces the wait time to transplantation for HCV+ patients. Direct-acting antiviral (DAA) therapy can cure HCV in virtually all who are infected. Some have suggested that treatment of HCV+ waitlisted patients be deferred with the hope that earlier transplantation will provide better outcomes than early DAA therapy. However, there are not enough organs to guarantee prompt transplantation for the current waitlist of infected candidates. A Markov medical decision analysis model was created to compare the overall outcomes of delayed DAA therapy (Option 1) to immediate DAA therapy (Option 2) in waitlisted HCV+ patients. Option 1 patients were modeled to be transplanted 1 year earlier, with a higher cumulative transplant incidence (54% at 5 years post-listing vs 45% for Option 2). Despite this, Option 2 provided 0.43 (95% confidence interval [CI] 0.38-0.49) more life years than Option 1. However, Option 1 was preferred for regions with much greater access to HCV+ organs or in patients with very low HCV+-associated mortality. The best option from an individual patient's perspective will differ by region and candidate.