Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

BACKGROUND: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. METHODS: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. RESULTS: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). CONCLUSIONS: Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.

Severity of COVID-19 among solid organ transplant recipients in Canada, 2020-2021: a prospective, multicentre cohort study.

BACKGROUND: Severe COVID-19 appears to disproportionately affect people who are immunocompromised, although Canadian data in this context are limited. We sought to determine factors associated with severe COVID-19 outcomes among recipients of organ transplants across Canada. METHODS: We performed a multicentre, prospective cohort study of all recipients of solid organ transplants from 9 transplant programs in Canada who received a diagnosis of COVID-19 from March 2020 to November 2021. Data were analyzed to determine risk factors for oxygen requirement and other metrics of disease severity. We compared outcomes by organ transplant type and examined changes in outcomes over time. We performed a multivariable analysis to determine variables associated with need for supplemental oxygen. RESULTS: A total of 509 patients with solid organ transplants had confirmed COVID-19 during the study period. Risk factors associated with needing (n = 190), compared with not needing (n = 319), supplemental oxygen included age (median 62.6 yr, interquartile range [IQR] 52.5-69.5 yr v. median 55.5 yr, IQR 47.5-66.5; p < 0.001) and number of comorbidities (median 3, IQR 2-3 v. median 2, IQR 1-3; p < 0.001), as well as parameters associated with immunosuppression. Recipients of lung transplants (n = 48) were more likely to have severe disease with a high mortality rate (n = 15, 31.3%) compared with recipients of other organ transplants, including kidney (n = 48, 14.8%), heart (n = 1, 4.4%), liver (n = 9, 11.4%) and kidney-pancreas (n = 3, 12.0%) transplants (p = 0.02). Protective factors against needing supplemental oxygen included having had a liver transplant and receiving azathioprine. Having had 2 doses of SARS-CoV-2 vaccine did not have an appreciable influence on oxygen requirement. Multivariable analysis showed that older age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07) and number of comorbidities (OR 1.63, 95% CI 1.30-2.04), among other factors, were associated with the need for supplemental oxygen. Over time, disease severity did not decline significantly. INTERPRETATION: Despite therapeutic advances and vaccination of recipients of solid organ transplants, evidence of increased severity of COVID-19, in particular among those with lung transplants, supports ongoing public health measures to protect these at-risk people, and early use of COVID-19 therapies for recipients of solid organ transplants.

Association of prevalent vascular disease with allograft failure and mortality in live-donor kidney transplant recipients - a retrospective cohort study.

Limited data exist regarding the impact of prevalent vascular disease after live-donor kidney transplantation. We aimed to determine the associations between the number of prevalent vascular diseases, allograft, and patient outcomes following live-donor transplantation. This cohort study used data from the Australia and New Zealand Dialysis and Transplant Registry. Rates between recipients of live-donor kidney transplants ± prevalent vascular disease prior to transplantation were calculated. The associations between vascular disease, allograft failure, and all-cause mortality were assessed using Cox regression modeling. Kaplan-Meier proportions were used to calculate all-cause mortality and death with a function graft stratified by vascular disease burden. Of 4742 live-donor recipients, 428 (9%) and 84 (2%) had prevalent vascular disease at 1 and ≥2 sites, respectively. Compared to recipients without vascular disease, the respective adjusted hazard ratios (95% confidence intervals) for patients with vascular disease at 1 and ≥2 sites were 1.78 (1.41-2.25) and 3.02 (2.03-4.50) for all-cause mortality; and 1.54 (1.26-1.88) and 2.28 (1.54-3.38) for allograft failure. All-cause mortality in recipients with vascular disease at 0, 1 and ≥2 sites was 0.028 (0.025, 0.031), 0.090 (0.073, 0.106) and 0.247 (0.196, 0.282) over the first 5-year post-transplant. There was an incremental association between the number of prevalent vascular disease sites and risk of allograft failure and all-cause mortality in live-donor kidney transplant recipients.

Outcomes of cinacalcet withdrawal in Australian dialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres. AIM: To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet. METHODS: We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24- and 12-month period, respectively, from cessation of cinacalcet. RESULTS: A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27-90) pmol/L to 85 (interquartile range 41-139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92-176) IU/L to 143 (102-197) IU/L (P < 0.0001). CONCLUSION: Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12-month period following withdrawal of cinacalcet. Longer-term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity.

Education Before Kidney Transplantation.

CONTEXT: Poor knowledge about immunosuppressive (IS) medications remains a major problem for patients in the posttransplant setting. Therefore, more effective educational strategies in the pretransplant setting are being considered as a possible method to improve knowledge and readiness for the challenges of posttransplant care. However, the most effective/relevant content of a pretransplant educational program is yet to be determined. OBJECTIVE: To identify pretransplant education topics from the posttransplant patient perspective. DESIGN: A focus group meeting was conducted among 7 high-functioning, stable adult kidney transplant recipients recruited from the Saskatchewan Transplant Program. Demographic information including age, gender, occupation, background/ethnicity, and time since transplant were recorded. A moderator, assistant moderator, and research assistant facilitated the 90-minute focus group meeting using a predetermined semistructured interview guide. The session was audio recorded and transcribed verbatim. Nvivo software was used to code the data and identify emerging themes exploring views of participants relating to the educational information required for pretransplant patients. RESULTS: Patients were satisfied with the education they had received. Ideas were classified into the following major themes-patient satisfaction, transplant waitlist, surgery, medications, posttransplant complications, lifestyle and monitoring, knowledge acquisition, illusion of control, and life changes posttransplant. Knowledge gaps were identified in all areas of the transplantation process and were not exclusive to IS medications. CONCLUSION: Misconceptions regarding transplantation were identified by a group of high-functioning, stable adult recipients who were satisfied with their clinical care. Future educational strategies should aim to address the entire transplantation process and not be limited to medications.

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients.

BACKGROUND: The Framingham risk score (FRS) and cardiovascular risk calculator for renal transplant recipients (CRCRTR-MACE) quantify cardiovascular risk in renal transplant recipients (RTR). In contrast to the FRS, the CRCRTR-MACE includes serum creatinine as a variable in the risk prediction equation. OBJECTIVE: To determine the influence of impaired renal function on performances of the two equations. METHODS: A chart review of 270 RTR transplanted from 1979 to 2012. High risk was defined at scores ≥20%. Standard statistical analyses included multivariate analysis (MVA), stepwise analysis, and odds ratio to estimate contributions of risk factors. RESULTS: Mean transplant duration was 9.51 ± 6.65 yr. Mean eGFR was 59.19 ± 28.26 mL/min/1.73 m(2) . FRS and CRCRTR-MACE scores of least 20% were present in 9.3% and 24.8%, respectively, while 7.2% and 11.2% of RTR with eGFR ≥60 mL/min/1.73 m(2) were high risk, respectively. Mean age, blood pressure, TC:HDL ratio, smoking, and diabetes were evenly distributed in patients with varying eGFR. FRS scores remained similar at wide eGFR range (≤30 mL/min/1.73 m(2) -≥90 mL/min/1.73 m(2) ), while CRCRTR-MACE scores significantly increased as eGFR decreased. CONCLUSIONS: CRCRTR-MACE identified more patients at high cardiovascular risk, even in those with more favorable renal function, suggesting a fundamental difference between the two calculators beyond renal function.

Waitlisted and Transplant Patient Perspectives on Expanding Access to Deceased-Donor Kidney Transplant: A Qualitative Study.

Background: A concerning number of kidneys (eg, expanded donor criteria, extended criteria, or marginal kidneys) are discarded yearly while patients experience significant morbidity and mortality on the transplant waitlist. Novel solutions are needed to solve the shortage of kidneys available for transplant. Patient perceptions regarding the use of these less than ideal kidneys remain unexplored. Objective: To explore the perspectives of patients who have previously received a less than ideal kidney in the past and patients awaiting transplant who could potentially benefit from one. Design: Qualitative description study. Setting: 2 provinces in Canada participated (Saskatchewan and Manitoba). Patients: Patients with end-stage kidney disease who were awaiting kidney transplant and were either (a) aged 65 years and older, or (b) 55 years and older with other medical conditions (eg, diabetes). Methods: Criterion sampling was used to identify participants. Semi-structured, one-on-one interviews were conducted virtually, which explored perceived quality of life, perceptions of less than ideal kidneys, risk tolerance for accepting one, and educational needs to make such a choice. The interviews were transcribed verbatim and thematic analysis was used to analyze the data. Results: 15 interviews were conducted with usable data (n = 10 pretransplant; n = 5 posttransplant). Participants were a mean of 65.5 ± 8.8 years old. Four interrelated themes became prominent including (1) patient awareness and understanding of their situation or context, (2) a desire for information, (3) a desire for freedom from dialysis, and (4) trust. Subthemes of transparency, clarity, standardization, and autonomy were deemed important for participant education. The majority of pretransplant participants (n = 8/10) indicated that between 3 and 5 years off of dialysis would make the risk of accepting a less than ideal kidney feel worthwhile. Limitation: The study setting was limited to 2 Canadian provinces, which limits the generalizability. Furthermore, the participants were homogenous in demographics such as ethnicity. Conclusion: These findings indicate that patients are comfortable to accept a less than ideal kidney for transplant in situations where their autonomy is respected, they are provided clear, standardized, and transparent information, and when they trust their physician. These results will be used to inform the development of a new national registry for expanding access to deceased-donor kidney transplant. Trial Registration: Not registered.

Contexte: De nombreux reins sont rejetés chaque année (donneurs à critères élargis, critères étendus ou reins marginaux), alors que les patients qui attendent une greffe présentent une morbidité importante et un taux de mortalité élevé. De nouvelles solutions sont nécessaires pour contrer la pénurie de reins disponibles pour une transplantation. Les perceptions des patients quant à l'utilization de ces reins moins idéaux restent inexplorées. Objectif: Explorer les perceptions des patients ayant reçu un rein moins idéal dans le passé et des patients en attente d'une greffe qui pourraient potentiellement bénéficier d'un tel don. Conception: Étude qualitative et descriptive. Cadre: Deux provinces canadiennes (Saskatchewan et Manitoba). Participants: Des patients atteints d'insuffisance rénale terminale en attente d'une transplantation (a) âgés de 65 ans et plus ou (b) âgés de 55 ans et plus et présentant d'autres problèmes de santé (ex. diabète). Méthodologie: L'échantillonnage avec critères a été utilisé pour identifier les participants. Des entretiens individuels semi-structurés menés virtuellement ont exploré la qualité de vie perçue, la perception quant aux reins moins idéaux, la tolérance à l'égard des risques inhérents à l'acceptation d'un tel rein, et les besoins d'information pour faire ce choix. Les entrevues ont été transcrites intégralement et l'analyze des données a été réalisée par analyze thématique. Résultats: Quinze entrevues avec données utilisables ont été menées (n = 10 avant la greffe; n = 5 après la greffe). Les participants avaient en moyenne 65.5 ± 8.8 ans. Quatre thèmes interreliés ont été dégagés : (1) la sensibilisation et la compréhension des patients quant à leur situation ou au contexte; (2) le besoin d'information; (3) le besoin d'un congé de dialyze; et (4) la confiance envers le médecin. La transparence, la clarté, la normalization et l'autonomie ont été jugées comme des sous-thèmes importants de l'éducation des participants. Pour la majorité des participants en attente d'une greffe (n = 8/10), l'idée d'un congé de 3 à 5 ans de dialyze rendrait acceptables les risques associés à l'acceptation d'un rein moins idéal. Limites: Étude tenue dans deux provinces canadiennes, ce qui limite la généralisabilité des résultats. Homogénéité des participants sur le plan démographique, notamment en ce qui concerne l'origine ethnique. Conclusion: Les résultats indiquent que les patients seraient à l'aise d'accepter un rein moins idéal pour une greffe, pourvu que leur autonomie soit respectée, qu'ils reçoivent des informations claires, standardisées et transparentes, et qu'ils aient confiance en leur médecin. Ces résultats serviront à éclairer l'élaboration d'un nouveau registre national afin d'élargir l'accès à la transplantation de rein provenant de donneurs décédés. Enregistrement de l'essai: Non enregistré.

Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared With Vaccinated Solid Organ Transplant Recipients: A Propensity Matched Cohort Study.

BACKGROUND: Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients. METHODS: We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes. RESULTS: From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients. CONCLUSIONS: SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population.

A Randomized Controlled Trial of a Pretransplant Educational Intervention in Kidney Patients.

Poor patient knowledge about transplantation is a significant problem following kidney transplant. A video-based educational intervention was developed to supplement standard education provided by transplant teams. METHODS: A multicenter randomized controlled trial tested the intervention delivered to patients undergoing assessment or waitlisted for kidney transplant. Adult participants were randomized to the control (standard education) or the intervention group, consisting of electronic access to the videos (or digital video disks if no internet) plus standard education. Differences between groups in changes in transplant knowledge (measured by the Kidney Transplant Understanding Tool), education satisfaction, self-efficacy, and quality of life (secondary outcomes) were evaluated by a preintervention and postintervention survey. Video viewing habits were tracked and described for patients in the intervention group. RESULTS: One hundred sixty-two patients were enrolled, with 132 completing both questionnaires (n = 64 intervention and n = 68 control), with similar enrollment from 3 Canadian sites. Video viewing statistics in the complete cases indicated that 78% (50/64) watched the videos, with 70% (45/64) viewing them electronically, while 8% (5/64) received digital video disks and self-reported participation. Baseline knowledge scores in the intent-to-treat population were 55.4 ± 6.5 and 55.7 ± 7.1 in the intervention and control, respectively. The mean knowledge change in the intervention (2.1 ± 3.6) was significantly higher than in the control group (0.8 ± 3.4, P < 0.02). In the per-protocol analysis (patients with objective evidence of watching at least 80% of the videos), the knowledge improvements were 3.4 ± 3.8. Video group participants reported higher satisfaction with education (P < 0.02) and expressed positive comments in open-ended feedback. CONCLUSIONS: Electronic video education in the pretransplant setting improved knowledge and satisfaction.

Clinical Practice Guideline for Solid Organ Donation and Transplantation During the COVID-19 Pandemic.

The coronavirus 2019 (COVID-19) pandemic has disrupted health systems worldwide, including solid organ donation and transplantation programs. Guidance on how best to screen patients who are potential organ donors to minimize the risks of COVID-19 as well as how best to manage immunosuppression and reduce the risk of COVID-19 and manage infection in solid organ transplant recipients (SOTr) is needed. METHODS: Iterative literature searches were conducted, the last being January 2021, by a team of 3 information specialists. Stakeholders representing key groups undertook the systematic reviews and generation of recommendations using a rapid response approach that respected the Appraisal of Guidelines for Research and Evaluation II and Grading of Recommendations, Assessment, Development and Evaluations frameworks. RESULTS: The systematic reviews addressed multiple questions of interest. In this guidance document, we make 4 strong recommendations, 7 weak recommendations, 3 good practice statements, and 3 statements of "no recommendation." CONCLUSIONS: SOTr and patients on the waitlist are populations of interest in the COVID-19 pandemic. Currently, there is a paucity of high-quality evidence to guide decisions around deceased donation assessments and the management of SOTr and waitlist patients. Inclusion of these populations in clinical trials of therapeutic interventions, including vaccine candidates, is essential to guide best practices.

Effect of N-acetylcysteine on serum creatinine and kidney function: results of a randomized controlled trial.

BACKGROUND: Evidence for a protective effect of N-acetylcysteine (NAC) on acute and chronic kidney disease is equivocal, and controversy persists about whether NAC affects creatinine level independently of actual kidney function. Study objectives are to investigate whether NAC affects serum creatinine level independently of alterations in other measures of kidney function. STUDY DESIGN: Double-blind randomized controlled trial. SETTING & PARTICIPANTS: Patients with stage 3 chronic kidney disease (n = 60), Canada, 2007-2008. INTERVENTION: Participants were randomly allocated to receive 4 doses of oral NAC (each 1,200 mg) or placebo, administered at 12-hour intervals. OUTCOME: The primary outcome was change in serum creatinine level between baseline and 4 hours after the last treatment dose. In addition, changes in other parameters of kidney function were measured between baseline and 4, 24, or 48 hours after the last treatment dose. MEASUREMENTS: Serum creatinine, cystatin C, 24-hour urine protein and creatinine excretion, and creatinine clearance. RESULTS: 60 patients, mean age of 70 years, 75% men, 50% had diabetes, with mean creatinine clearance of 43.7 ± 18.8 (SD) mL/min were enrolled. Between baseline and 4 hours posttreatment, serum creatinine level decreased by 0.044 ± 0.15 mg/dL in the NAC group and 0.040 ± 0.18 mg/dL in the placebo group (95% CI for difference, -0.09 to 0.08; P = 0.9). No significant differences between groups were observed for change in serum creatinine, cystatin C, urine protein, urine creatinine, or creatinine clearance values at any time. LIMITATIONS: Blinding patients to orally administered liquid NAC is difficult and it is possible that patients receiving NAC were not sufficiently blinded. Effects of NAC beyond 48 hours of treatment were not evaluated. CONCLUSIONS: In this randomized controlled trial, NAC had no short-term effect on creatinine level and did not decrease urine protein excretion within 48 hours of treatment.

A RAND-Modified Delphi on Key Indicators to Measure the Efficiency of Living Kidney Donor Candidate Evaluations.

BACKGROUND AND OBJECTIVES: Many patients, providers, and potential living donors perceive the living kidney donor evaluation process to be lengthy and difficult to navigate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We sought consensus on key terms and process and outcome indicators that can be used to measure how efficiently a transplant center evaluates persons interested in becoming a living kidney donor. Using a RAND-modified Delphi method, 77 participants (kidney transplant recipients or recipient candidates, living kidney donors or donor candidates, health care providers, and health care administrators) completed an online survey to define the terms and indicators. The definitions were then further refined during an in-person meeting with ten stakeholders. RESULTS: We identified 16 process indicators (e.g., average time to evaluate a donor candidate), eight outcome indicators (e.g., annual number of preemptive living kidney donor transplants), and two measures that can be considered both process and outcome indicators (e.g., average number of times a candidate visited the transplant center for the evaluation). Transplant centers wishing to implement this set of indicators will require 22 unique data elements, all of which are either readily available or easily collected prospectively. CONCLUSIONS: We identified a set of indicators through a consensus-based approach that may be used to monitor and improve the performance of a transplant center in how efficiently it evaluates persons interested in becoming a living kidney donor.

Canadian Society of Transplantation and Canadian Society of Nephrology Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

PURPOSE OF REVIEW: To review an international guideline on the evaluation and care of living kidney donors and provide a commentary on the applicability of the recommendations to the Canadian donor population. SOURCES OF INFORMATION: We reviewed the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors and compared this guideline to the Canadian 2014 Kidney Paired Donation (KPD) Protocol for Participating Donors. METHODS: A working group was formed consisting of members from the Canadian Society of Transplantation and the Canadian Society of Nephrology. Members were selected to have representation from across Canada and in various subspecialties related to living kidney donation, including nephrology, surgery, transplantation, pediatrics, and ethics. KEY FINDINGS: Many of the KDIGO Guideline recommendations align with the KPD Protocol recommendations. Canadian researchers have contributed to much of the evidence on donor evaluation and outcomes used to support the KDIGO Guideline recommendations. LIMITATIONS: Certain outcomes and risk assessment tools have yet to be validated in the Canadian donor population. IMPLICATIONS: Living kidney donors should be counseled on the risks of postdonation outcomes given recent evidence, understanding the limitations of the literature with respect to its generalizability to the Canadian donor population.

JUSTIFICATION: Examiner une directive internationale sur l'évaluation et la prise en charge des donneurs vivants d'un rein et formuler un commentaire sur l'applicabilité de ces recommandations à la population des donneurs canadiens. SOURCES: Nous avons révisé le guide des pratiques cliniques relatives à l'évaluation et à la prise en charge des donneurs vivants d'un rein (Clinical Practice Guideline for Evaluation and Care of Living Kidney Donors) de 2017 du KDIGO (Kidney Disease: Improving Global Outcomes) et nous l'avons comparé aux recommandations canadiennes de 2014 du Protocole de don croisé d'un rein par donneurs participants (Kidney Paired Donation Protocol for Participating Donors). MÉTHODOLOGIE: Un groupe de travail réunissant des membres de la Société canadienne de transplantation et de la Société canadienne de néphrologie a été formé. Les membres ont été sélectionnés pour représenter tout le Canada et plusieurs sous-spécialisations relatives au don vivant d'un rein, notamment la néphrologie, la chirurgie, la transplantation, la pédiatrie et l'éthique. PRINCIPALES CONSTATATIONS: Plusieurs des recommandations du KDIGO s'harmonisent aux recommandations du protocole de don croisé d'un rein. Les chercheurs canadiens ont contribué en grande partie aux données sur l'évaluation des donneurs et des résultats utilisées pour appuyer les recommandations formulées dans les lignes directrices du KDIGO. LIMITES: Certains résultats et outils d'évaluation des risques doivent encore être validés dans la population des donneurs canadiens. CONCLUSION: Compte tenu des plus récentes données, les donneurs vivants d'un rein devraient être mis en garde concernant les risques sur leur santé post-don, tout en comprenant les limites de la littérature en ce qui concerne leur généralisabilité à la population de donneurs canadiens.

Review article: Managing bone complications after kidney transplantation.

Chronic kidney disease mineral and bone disorder (CKD-MBD) describes the laboratory, bone and vascular abnormalities that exist in patients with CKD stages 3-5D and that may persist after transplantation. Persisting abnormalities of bone turnover and abnormal mineralization, together with bone mineral density (BMD) loss from glucocorticoids, may all predispose to a loss of structural integrity and increased fracture risk in kidney and kidney pancreas recipients. Vitamin D, calcitriol, calcitonin and bisphosphonates have all been used to preserve BMD following transplantation, despite a lack of safety data and the potential for some of these drugs to cause harm. A limited number of post-transplant studies utilizing these drugs have not yet documented improved fracture prevention or fracture-related mortality and have not considered allocation based on risk factors for fracture or markers of bone turnover. Targeted allocation of the available therapies based on a stratification of risk appears warranted. This might be achieved using an algorithm incorporating BMD, X-ray evaluation, laboratory investigations including bone turnover markers and the assessment of standard fracture risk factors at the time of and soon after transplantation. This approach, which is similar to protocols used in the general population, may result in more effective management of patients and fewer adverse effects such as adynamic bone disease. Although BMD is a surrogate for fracture risk in the general population it is not validated in this transplant population. Consequently, such an approach should be confirmed by studies that include bone biopsy data and an evaluation of patient level outcomes.

Randomised controlled trial of a video intervention and behaviour contract to improve medication adherence after renal transplantation: the VECTOR study protocol.

INTRODUCTION: Non-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers' time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications. METHODS AND ANALYSIS: A multicentre, parallel arm, randomised controlled trial will be conducted with four sites across North America (Saskatoon, Calgary, Halifax, Chicago). Adult patients will be randomised (1:1) to either the intervention (ie, home-based video education +behaviour contract plus usual care) or usual care alone. De novo transplant recipients will be enrolled prior to their hospital discharge and will be provided with electronic access to the video intervention (immediately) and adherence contract (1 month post-transplant). Follow-up electronic surveys will be provided at 3 and 12 months postenrolment. The primary outcome will be adherence at 12 months post-transplant, as measured by self-report Basel Assessment of Adherence to Immunosuppressive medications and immunosuppressant levels. Secondary outcomes include the difference in knowledge score between the intervention and control in groups (measured by the Kidney Transplant Understanding Tool); differences in self-efficacy (Generalised Self-efficacy Scale), Beliefs of Medicine Questionnaire (BMQ), quality of life (Short Form-12), patient satisfaction and cost utilisation. The study aims to recruit at least 200 participants across participating sites. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Saskatchewan Behavioural Ethics Committee (Beh 18-63), and all patients provide informed consent prior to participating. This educational intervention aims to improve information retention and self-efficacy, leading to improved medication adherence after kidney transplantation, at low cost, with little impact to existing healthcare personnel. If proven beneficial, delivery can be easily implemented into standard of care. TRIAL REGISTRATION NUMBER: NCT03540121; Pre-results.

Development of a patient-centered video series to improve education before kidney transplantation.

BACKGROUND: Inadequate patient knowledge about transplantation can result in low patient satisfaction and contribute to poor clinical outcomes. The purpose of this patient-oriented research project was to develop an educational intervention for patients awaiting kidney transplantation. METHODS: An educational intervention was developed by patients and health care providers, experts in medication adherence, video education, motivational psychology, and cultural education. Project objectives were defined and content was guided by a series of studies conducted with stakeholders. A review process was undertaken with additional patients, external health care providers and ninth grade high school students and edits were applied accordingly. RESULTS: A set of six educational videos, ranging in length from 3 to 24 min, was created to describe the transplant process. The videos are patient friendly in design, and incorporate animations to explain complex information to accommodate low health literacy, and patient testimonials align the content with principles of adult learning theory. Feedback from external patient reviews [n = 8], external care providers [n = 13] and students [n = 26], indicate that the mini-series is informative and useful. CONCLUSION: Patient involvement significantly influenced the development of a video series about kidney transplantation. PRACTICE IMPLICATIONS: Patient engagement is integral for developing high quality and relevant educational interventions.

Development and Validation of the Kidney Transplant Understanding Tool (K-TUT).

BACKGROUND: Several educational interventions have been designed to improve patient knowledge before and after kidney transplantation. However, evaluation of such interventions has been difficult because validated instruments to measure knowledge-based outcomes in this population have not been developed. OBJECTIVE: To create a tool to measure patient knowledge of kidney transplantation and to evaluate its validity. METHODS: The Kidney Transplant Understanding Tool (K-TUT) was created using a stepwise iterative process. Experts in the field and transplant recipients were consulted to establish content validity. The K-TUT consists of 9 true/false and 13 multiple-choice questions, and scores are based on the number correct answers [YES/NO format] of 69 items. The questionnaire was piloted in a study that also measured health literacy (via the Short Test of Functional Health Literacy) in transplant candidates, whereas the main survey was mailed to transplant recipients. Test-retest was performed, and completed surveys were analyzed for internal consistency, construct validity, floor and ceiling effects, and reproducibility. RESULTS: Surveys were offered to 106 pretransplant patients and 235 in the posttransplant period, and response rates were 38.7% (41/106) and 63.4% (149/235), respectively. The mean corrected scores were 53.1 ± 8.5 (77%) and 56.2 ± 6.3 (81%), respectively. Test-retest was performed over 20% of both cohorts and percent agreement ranged between 70% and 100% in the pretransplant group and 66% and 100% in the posttransplant group. Cronbach α ranged from 0.794 to 0.875 in all cohorts indicating favorable internal consistency. Increased health literacy in the pretransplant group was significantly associated with increased knowledge (r = 0.52; P < 0.001), suggestive of construct validity, and the absence of floor and ceiling effects was positive. The majority of transplant recipients (98/148, 67%) believed the questionnaire adequately assessed transplant knowledge, about a quarter (36/148, 24.3%) were "unsure," and 85% (126/148) agreed that no questions should be removed. CONCLUSIONS: Although more study is warranted to further assess psychometric properties, the K-TUT appears to be a promising tool to measure transplant knowledge.

Trimethoprim-sulfamethoxazole-associated hepatotoxicity - part of a hypersensitivity syndrome.

Trimethoprim-sulfamethoxazole is a commonly used medication. Side effects are numerous and include drug hypersensitivity syndrome. The case of a 24-year-old woman with severe liver failure is presented. Erythema multiforme and thrombocytopenia developed after the acute onset of hepatotoxicity and after all medications had been stopped. Clinical resolution of all features occurred over weeks but laboratory abnormalities persisted up to eight months later. A causal link with sulfamethoxazole was supported by timing, liver biopsy and lymphocyte toxicity test. This case illustrates one presentation and the possible severity of the drug hypersensitivity syndrome associated with trimethoprim-sulfamethoxazole.