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.

Health Literacy, Knowledge, and Patient Satisfaction Before Kidney Transplantation.

BACKGROUND: Poor health literacy is associated with inferior outcomes in kidney transplant recipients, and knowledge remains suboptimal in this population. The goal of this study was to characterize the health literacy, kidney transplant knowledge, medication beliefs, and education satisfaction in a cohort of patients waiting to undergo kidney transplantation. METHODS: All patients on the wait-list in 1 Canadian center were invited to participate in the study. A research assistant administered the Short Test of Functional Health Literacy in Adults and its numeracy section, the Beliefs about Medicines Questionnaire, the Kidney Transplant Understanding Tool, and questions regarding satisfaction. Descriptive and univariate statistics were calculated between demographic variables and the assessments. RESULTS: Thirty-nine percent of patients (41 of 106) patients participated in the study. Overall, 95% and 86% were defined as having adequate health literacy and numeracy, respectively. The mean score on the Kidney Transplant Understanding Tool was 79%, and the majority (97.4%) had strong beliefs regarding the necessity of medication and little concern about adverse effects (73.8%). Participants with higher literacy scores had increased knowledge (r = 0.52; P = .05), understanding of why antirejection pills are necessary (r = 0.38; P = .05), and confidence about taking posttransplant medications (r = 0.32; P = .05). Overall, 30.7% were unsatisfied with their education regarding medications, and 22.5% were unsatisfied with what to expect after the transplant. CONCLUSIONS: Before transplantation, health literacy, transplant knowledge, and scores on the Beliefs about Medicines Questionnaire were high in this cohort of patients. However, patient satisfaction regarding educational content remained suboptimal.

Prevention of recurrent cerebral ischemic events in patients with patent foramen ovale and cryptogenic strokes or transient ischemic attacks.

BACKGROUND: Patent foramen ovale (PFO) is found in up to 50% of patients less than 55 years of age who have had a stroke. Therapeutic options include no therapy, antiplatelet therapy, warfarin and surgical closure of the PFO. OBJECTIVES: To determine the relative and attributable risks of PFO for recurrent cerebral ischemic events in young patients with stroke or transient ischemic attacks. The predictors of recurrent cerebral ischemic events and the effects of different therapies on recurrence rates were sought. DESIGN: Follow-up of a retrospective cohort of patients with cryptogenic stroke or transient ischemic attacks identified from an echocardiography database. SETTING: University-based regional neurology referral centre. PATIENTS: Consecutive group of 90 patients less than 60 years of age who underwent transesophageal echocardiography following a cryptogenic transient ischemic attack (TIA) or stroke (cerebrovascular accident [CVA]) between 1991 and 1997. INTERVENTIONS: Structured telephone interviews and chart reviews. RESULTS: Fifty-two patients had a PFO, and 38 patients did not have a PFO. During a mean follow-up of 46 months, 19 recurrent cerebral ischemic events (12 TIA and seven CVA) occurred in 14 patients with PFO, and eight recurrent events (three TIA and five CVA) occurred in six patients without PFO. The recurrence rates were 12% and 5%/patient/year in the PFO and control groups, respectively, for a crude recurrence rate ratio of 2.39 (95% CI 1.01 to 6.32, P < 0.03). The attributable risk of PFO in recurrent neurological events was 7%/patient/year. In a Cox regression model, predictors of recurrent neurological events were presence of PFO (hazard ratio 5.27, 95% CI 1.58 to 17.6, P < 0.007), history of migraine (hazard ratio 4.54, 95% CI 1.11 to 18.52, P < 0.035), hypertension requiring therapy (hazard ratio 3.5, 95% CI 1.33 to 9.01, P < 0.01), and antiplatelet or no therapy instead of warfarin therapy (hazard ratio 2.88, 95% CI 1.11 to 8.7, P < 0.04). Fourteen patients underwent surgical closure of PFO; there were no neurological recurrences during a mean follow-up of 43 months (crude incidence rate difference 12%/patient/year, 95% CI 6.6 to 17.9, P < 0.02). CONCLUSIONS: Patients with PFO had a significantly higher rate of recurrent cerebral ischemic events than those without PFO. Surgical PFO closure prevented any recurrences during a mean follow-up of 43 months. Warfarin was better than antiplatelet therapy or no therapy in preventing recurrences.

Severe antibody-mediated rejection following IVIG infusion in a kidney transplant recipient with BK-virus nephropathy.

Intravenous immune-globulin (IVIG) use in renal transplantation has increased, with common uses including desensitization, treatment of antibody mediated rejection and adjunctive therapy for BK virus nephropathy. Although considered generally safe, potential side effects can occur in up to 23% of patients including acute kidney injury. We present a case of an unexpected cause of acute kidney injury in a renal transplant recipient following IVIG infusion. A 48-year-old nonsensitized female with end stage renal disease secondary to polycystic kidney disease received a deceased donor kidney transplant. The initial post-transplant period was unremarkable however at three years post-transplant the patient develops BK virus nephropathy. Despite a reduction in immunosuppression, graft function worsened and IVIG infusion was commenced. Immediately following the IVIG infusion, the patient develops anuric acute kidney injury necessitating hemodialysis. Renal transplant biopsy performed before and after the IVIG infusion revealed the de novo development of acute antibody mediated rejection and donor specific antibodies in the serum. Anti-HLA and donor-specific antibodies were also confirmed in a diluted sample of the IVIG preparation. We argue that the anti-HLA antibodies present in the IVIG caused an acute antibody mediated rejection in this previously nonsensitized female.

Differential nature of cross-talk among three G-coupled receptors regulating adenylyl cyclase in rat cardiomyocytes chronically exposed to receptor agonists.

Chronic exposure of cells to cognate agonists has been established to cause homologous desensitization of G protein-coupled receptors. In this work, we show that exposure of adult rat cardiomyocytes to isoproterenol (ISO) for 24 h led to the desensitization of beta-adrenoceptor (beta-AR) coupled adenylyl cyclase (AC) activity, which was associated with an increased inhibition of AC by M2-muscarinic receptor (MR) agonist, carbachol (Cch), and a decreased inhibition of AC by A1-adenosine receptor (AdR) agonist, N6-phenylisopropyladenosine (R-PIA). Chronic exposure of cells to Cch caused the desensitization of M2-MR-coupled AC, decreased the inhibitory action of R-PIA on AC and increased ISO-stimulated AC, while chronic exposure to R-PIA caused the desensitization of A1-AdR-coupled AC and modestly increased ISO-stimulated AC without any significant effect on Cch inhibition of the enzyme. Thus, chronic exposure of cardiomyocytes revealed for the first time a more complex and differential nature of cross-talk among the three major G-coupled receptors in modulating AC.

Expressed alpha 1-adrenoceptors in adult rat brown adipocytes are primarily of alpha 1A subtype.

The main objective of this study was to characterize the alpha 1-adrenoceptors expressed in adult rat brown adipocytes. For this purpose, membrane fractions were prepared from brown adipose tissue as well as from isolated brown adipocytes. The following are major findings: (i) BAT membranes were considerably enriched in alpha 1-adrenoceptors (specific [3H]prazosin binding, Bmax, 79.49 +/- 16.77 fmol/mg protein; KD, 0.24 +/- 0.04 nM); (ii) among the cells that comprise brown adipose tissue, brown adipocytes were enriched in alpha 1-adrenoceptors; (iii) > 95% of total alpha 1-adrenoceptors were resistant to inactivation by 20 microM chloroethylclonidine, which readily and essentially completely inactivated alpha 1B-adrenoceptors in rat liver membranes; (iv) brown adipose tissue membrane alpha 1-adrenoceptors showed high affinity towards 5-methyl urapidil (KD 7.23 +/- 2.49 nM) and WB 4101 (KD 0.66 +/- 0.30 nM) and low affinity towards BMY 7378 (KD 0.34 +/- 0.03 microM); essentially similar affinities for these drugs were seen for membranes prepared from brown adipocytes; and (v) EBDA/LIGAND analysis of 5-methyl urapidil, WB 4101, and BMY 7378 competition curves revealed the presence of a single binding site for these drugs. Recent work has documented that 5-methyl urapidil and WB 4101 interact with high affinity with alpha 1A-adrenoceptors, while BMY 7378 interacts with high affinity with alpha 1D-adrenoceptors. Taken together, these findings are consistent with the view that alpha 1-adrenoceptors expressed in adult rat BAT are mainly of the alpha 1A subtype.

Alterations in inotropy, nitric oxide and cyclic GMP synthesis, protein phosphorylation and ADP-ribosylation in the endotoxin-treated rat myocardium and cardiomyocytes.

To evaluate the effects of the in vivo endotoxin treatment of the rat on (1) the contractile responses in the subsequently isolated papillary muscle to adrenergic and cholinergic agonists and (2) the biochemical parameters (cyclic GMP, nitric oxide synthesis, protein phosphorylation and ADP-ribosyslation) in the subsequently isolated cardiomyocytes. Following the in vivo endotoxin treatment (4 mg/kg i.p., 18 h), contractile responses to increasing amounts of isoprenaline or to increasing amounts of oxotremorine in the presence of a fixed amount of isoprenaline were determined in isolated papillary strips. Activities of nitric oxide synthase, guanylyl cyclase, as well as phosphorylation of phospholamban and troponin-inhibitory subunit, and pertussis toxin-catalyzed and endogenous ADP-ribosylations were determined in the intact cardiomyocytes and subcellular fractions. The increase in the force of contraction by isoprenaline was reduced, while its inhibition by oxotremorine was greater in the endotoxin-treated papillary strips. The activities of both nitric oxide synthase, primarily of the inducible form of the enzyme, and cytosolic guanylyl cyclase were higher while the phosphorylations of both phospholamban and troponin-inhibitory subunit were of lesser magnitude in the cardiomyocytes following the in vivo endotoxin treatment. Pertussis toxin-catalyzed ADP-ribosylation of the 41 kDa polypeptide, which is the alpha subunit of Gi, was also decreased. The results of the present study support the postulate that alterations in both the cyclic AMP and cyclic GMP signalling cascade contribute to the myocardial dysfunction caused by endotoxin and cytokines.