Evolving trends in immunosuppression use and cytomegalovirus infection risk over the past decade in kidney transplantation.

BACKGROUND: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years. METHODS: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses. RESULTS: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection. CONCLUSION: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration.

COVID-19 and renal allograft rejection: insight from controlled and non-controlled studies.

AIM: Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). METHODS: This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: 'COVID', 'Renal', 'Kidney', 'Transplant', and 'Rejection'. The results from controlled and uncontrolled studies were separately collated and analyzed. RESULTS: A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. CONCLUSION: In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

Peer-reviewed visuals and auditory - isn't it time to incorporate?

A remarkable opportunity emerges amidst the dynamic evolution of medical education, one that could fundamentally alter how healthcare professionals gain and share knowledge. The concept of incorporating a structured, peer-reviewed video and audio section, as well as a dedicated submission portal, into the medical journals symbolizes a revolutionary advance. This addition has the potential to not only improve the educational experiences of the journal's audience, but also to create a more accessible forum for the exchange of knowledge and citation. In this article, we explore the compelling potential of introducing structured videos and podcasts into the domain of medical literature, as well as the promising implications for revamping medical practitioners' learning strategies.

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Hyperkalemia in chronic peritoneal dialysis patients.

Background. Chronic peritoneal dialysis (PD) patients often develop hypokalemia but less commonly hyperkalemia.Methods. We explored incidence and mechanisms of hyperkalemia in 779 serum samples from 33 patients on PD for 1 - 59 months. Normal serum potassium concentration was defined as 3.5 - 5.1 meq/l.Results. Mean monthly serum potassium concentrations were normal (except for 1 month), but we observed hypokalemia (<3.5 meq/l) in 5% and hyperkalemia (>5.1 meq/l) in 14% of 779 serum samples. Incidence of hyperkalemia did not change over time on PD: Year 1 (15%), Year 2 (11%), Year 3 (19%), Years 4-5 (22%). Hyperkalemia was mostly modest but occasionally extreme [5.2-5.4 meq/l (55%), 5.5-5.7 meq/l (21%), 5.8-6.0 meq/l (10%), >6.0 meq/l (14%)]. Of 31 patients (2 excluded due to brief PD time), 39% displayed hyperkalemia only, 23% displayed hypokalemia only, and the remainder (38%) displayed both or neither. Comparing hypokalemia-only with hyperkalemia-only patients, we found no difference in potassium chloride therapy, medications interrupting the renin-angiotensin system, small-molecule transport status, and renal urea clearance. We compared biochemical parameters from the hypokalemic and hyperkalemic serum samples and observed lower bicarbonate concentrations, higher creatinine concentrations, and higher urea nitrogen concentrations in the hyperkalemic samples (p < 0.001 for each), without difference in glucose concentrations.Conclusion. We observed hyperkalemia 3 times as frequently as hypokalemia in our PD population. High-potassium diet, PD noncompliance, increased muscle mass, potassium shifts, and/or the daytime period without PD might contribute to hyperkalemia.

Investigating the Synergistic Interactions of Surface Immobilized and Free Natural Ocular Lubricants for Contact Lens Applications: A Comparative Study between Hyaluronic Acid and Proteoglycan 4 (Lubricin).

The main reasons for the discontinuation of contact lens wear are ocular dryness and discomfort. Proteoglycan 4 (PRG4), a mucinous glycoprotein, and hyaluronic acid (HA), a nonsulfated linear glycosaminoglycan, are naturally present in the eye and contribute to ocular hydration and lubrication. This study aimed to investigate the impact of the structure of the recombinant human PRG4 (rhPRG4)/HA complex on contact lens properties, when one agent is grafted and the counterpart is physisorbed on the surface of model conventional or silicone contact lens materials. Investigation of the wettability, water retention, antifouling, and boundary lubricant properties of the prepared hydrogels showed that the rhPRG4/HA interactions varied with the rhPRG/HA configuration on the hydrogel surface as well as the composition of the underlying substrate used. The rhPRG4-physisorbed/HA-grafted sample was characterized by better antifouling and boundary lubricant properties on the model conventional hydrogels, while the HA-physisorbed/rhPRG4-grafted sample exhibited improved surface wettability, antifouling, and water-retentive properties on the model silicone hydrogels. The results of this study contribute to the design of biomimetic contact lens surfaces that work synergistically with ocular fluid-phase biological agents to enhance compatibility between the contact lens and the ocular environment, alleviating dry eye symptoms and improving comfort.

How We Got Where We Are in Blood Pressure Targets.

PURPOSE OF REVIEW: While we started clinical trials evaluating the benefit of lowering systolic BP's >160 mm Hg and diastolic BPs of <130 mm Hg, the latest guideline suggests a target of <130/80 mm Hg in those with hypertension. This article summarizes exactly how we got to where we are looking over the last half-century. RECENT FINDINGS: Our understanding of systolic and diastolic blood pressure targets to improve cardiovascular outcomes has changed substantially over the past 5 decades. Regarding diastolic blood pressure targets to improve cardiovascular outcomes, initially the VA1 in 1967 had set the goal to <115 mmHg. Over time, several studies including the VA2, Hypertension Optimal Treatment (HOT), and United Kingdom Prospective Diabetes Study Group 38 (UKPDS38) highlighted even greater cardiovascular benefit with lower diastolic targets <80 mmHg, especially in diabetic patients. Of equal importance, multiple studies have focused the attention to systolic blood pressure targets. Starting in 1948 with the Framingham study, passing through the Systolic Hypertension in the Elderly Program (SHEP), Syst-Eur and Syst-China trials, all have set the systolic blood pressure goal <150 mmHg. Most recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an improved cardiovascular outcome with a systolic blood pressure target <140 mmHg in patients with type 2 diabetes, while the Systolic Blood Pressure Intervention Trial (SPRINT) in non-diabetic patients moved it closer to 120 mmHg. There is "no one size fits all" when it comes to blood pressure targets to improve cardiovascular outcomes. To progress our understanding of individual blood pressure goals, future studies might develop a more standardized approach to highlight characteristics such as design and end point definitions while allowing clinical practitioners greater latitude to adapt guideline recommendations to individual patient characteristics and clinical needs.

Retrospective analysis of nontraumatic subdural hematoma incidence and outcomes in Egyptian patients with end-stage renal disease on hemodialysis.

BACKGROUND: The incidence of subdural hematoma (SDH) in chronic maintenance hemodialysis (CMH) patients may change over time, along with the evolving characteristics of the underlying populations. METHODS: We conducted a retrospective, single-center study at Cairo University hospitals, assessing the incidence, associated risk factors, and outcomes of nontraumatic SDH in CMH patients between January 2006 and January 2019. RESULTS: Out of 1217 CMH patients, nontraumatic SDH was diagnosed in 41 (3.37%) during the study, increasing with the enrollees' age but stable over the observation period and translating into an annual incidence rate of 28 per 1000 patients per year. SDH patients were likely to use central venous catheters, reported pruritis and history of bone fractures, and had higher phosphorus, parathyroid hormone, and alkaline phosphatase values (p < 0.001); however, there was no association with atrial fibrillation or use of anticoagulants. In the SDH cohort (n = 41), six patients did not need surgical intervention and 13 patients died before becoming surgically fit for intervention; mortality correlated with ischemic heart disease (p = 0.033) and the presence of atrial fibrillation or chronic anticoagulation with warfarin (p < 0.0001 for both), among others. Twenty-two patients received surgical operations and of these 2 died postoperatively; overall patient mortality was 12/41 (29.27%) at 30 days and 15/41 (36.59%) at 1 year. CONCLUSION: Our study demonstrated a striking enrichment for underlying comorbidities in those patients developing SDH and a high risk of immediate mortality. The benefit of chronic anticoagulation therapy should be carefully weighed against the risk of CNS bleed in MHD patients.

Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.

Phenotype of immunosuppression reduction after kidney transplantation.

BACKGROUND: Immunosuppressive regimens are delivered without direct measure of the net state of immunosuppression. Besides therapeutic drug monitoring, adjustments in immunosuppressive medications are largely event-driven. METHODS: We studied the clinical phenotype of immunosuppression reduction (ISR) among kidney transplant recipients from 2005 to 2012. Patients were grouped into: no ISR, ISR for infection, or ISR for intolerance. Outcome measures were rejection, rejection-free survival, and IFTA-free survival. RESULTS: 1114 adult kidney transplant recipients were included: 57% had no ISR, 16% had ISR for infection, and 27% had ISR for intolerance. ISR for infection was mainly on MMF, while ISR for intolerance was mainly on FK. ISR was associated with higher rates of acute rejection. The Kaplan-Meier analysis showed increased prevalence of rejection among patients with ISR due to infection (P = .003) or intolerance (P = .05). The risk of interstitial fibrosis and tubular atrophy was increased in patients with ISR due to infection (P = .001) or intolerance (P = .018). CONCLUSION: Immunosuppression reduction is associated with increased prevalence of rejection. The clinical phenotype of ISR is dominated by IFTA remote from the onset of ISR. Solely focusing on acute rejection may underestimate effects of ISR on long-term graft function and survival.

Eosinophilia and risk of incident end stage kidney disease.

BACKGROUND: Eosinophils in kidney disease are poorly understood and are often incidental findings on kidney biopsy. Eosinophilia in blood and renal biopsy tissue is associated with a host of immune and non-immune kidney diseases. The significance of eosinophilia in renal diseases has not been well addressed. We evaluated the presence of peripheral eosinophilia (> 4% of blood leukocytes) with biopsy tissue eosinophilia and their association with end-stage-kidney-disease (ESKD). METHODS: A nested case-control (2:1) of patients who underwent kidney biopsies at Johns Hopkins Hospital and Medical University of South Carolina from 2004 to 2018 were included in the study. From the 616 eligible patients, 178 patients were identified through the registry of kidney biopsies as 18 years or older without missing biopsy reports or hematology results. Controls (n = 154) had no ESKD at the time of case (n = 24) designation and were assembled using incident density sampling and matched on age and sex. The association of peripheral eosinophilia (> 4% of peripheral blood leukocytes) with the risk of progression to ESKD was evaluated using conditional logistic model after adjusting for clinical demographics. RESULTS: Among 178 patients, 65 (37%) had peripheral eosinophilia and 113 (63%) had no eosinophilia. Compared to patients without eosinophilia, patients with peripheral eosinophilia were notably male and had a higher serum creatinine at the time of their biopsy. Peripheral eosinophilia was associated with higher risk of ESKD (OR 15.9 [1.9, 134.7]) adjusted for patient demographics including hypertension, proteinuria and eGFR at the time of kidney biopsy. Peripheral eosinophilia had a significant linear association with kidney tissue eosinophils, 22 (standard deviation [SD] 20) per high power field (hpf) in 4-10% peripheral eosinophilia, 19 (SD 18) per hpf in ≥10% eosinophilia and 3 (SD 7) per hpf in no eosinophilia (P <  0.001). CONCLUSIONS: Peripheral eosinophilia is an independent predictor of tissue eosinophilia and subsequent progression to ESKD. Peripheral eosinophilia may be an early biomarker for underlying inflammation and disease, but further studies to investigate this clinical association are warranted.

Renal allograft surveillance with allospecific T-cytotoxic memory cells.

BACKGROUND: Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in "for cause" biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater. METHODS: The performance of allospecific TcM was evaluated retrospectively in primary renal transplant recipients (RTR) at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Twenty-two primary RTR, median age 45 years (range 19-72) were tested with allospecific CD154 + TcM. Samples were obtained at the mean ± SD time interval of 806 ± 239 days after kidney transplantation. Six of 22 patients experienced biopsy proven T- Cell Mediated Rejection (TCMR). A seventh showed antibody mediated rejection (ABMR). Of these seven patients six demonstrated increased likelihood of rejection with allospecific TcM (sensitivity 83%). Ten of these 15 patients with no rejection had a negative test (specificity 67%). False positive tests were seen in five patients. Six out of 11 patients with positive tests had ACR/ABMR with a PPV of 54%, while 10 out of 11 patients with negative tests were non-rejecters with a NPV of 91%. CONCLUSION: Allospecific T-cytotoxic memory cells distinguished primary RTR with quiescent allografts from those with dysfunction. With serial surveillance measures, this test system may facilitate decisions to manage immunosuppression in RTR.

Relationship between rabbit anti-thymocyte globulin and development of PTLD and its aggressive form in renal transplant population.

Introduction: The aim of our study is to explore the relationship of rabbit anti-thymocyte globulin (R-ATG) on development of post-transplant lymphoproliferative disease (PTLD) and its aggressive forms (monomorphic PTLD and Hodgkin lymphoma) in renal transplant recipients.Methodology: All patients diagnosed with PTLD post-renal transplant in the United States' Organ Procurement and Transplantation Network from 2003 till 2013 and followed up till 2017 were retrospectively reviewed. Multi-variable logistic regression analysis assessed association of R-ATG to development of PTLD and its aggressive form.Results: Risk of developing PTLD post renal transplant is 1.35%. In comparison to interleukin-2 blocker induction therapy, R-ATG is associated with increased risk of development of PTLD (Odds Ratio = 1.48, confidence interval ranges from 1.04 to 2.11, p = .02) and is associated with higher risk of development of aggressive PTLD (Odds Ratio = 1.83, confidence interval ranges from 1.001 to 3.34, p = .04).Conclusion: We conclude that R-ATG induction is associated with a higher risk of PTLD and its aggressive form (monomorphic PTLD and Hodgkin lymphoma). Careful monitoring for development of PTLD in renal transplant recipients receiving R-ATG induction therapy is advised.

Diffuse membranoproliferative glomerulonephritis with focal sclerosis and renal amyloidosis in an adult male with autosomal dominant dystrophic epidermolysis bullosa: a case report.

Previous reports of glomerular disease in adult patients with autosomal dominant dystrophic epidermolysis bullosa (EB) are limited and include post-infectious glomerulonephritis, IgA nephropathy, amyloidosis, and leukocytoclastic vasculitis. To our knowledge, membranoproliferative glomerulonephritis (MPGN) has not been described before. We report a case of a 39-year-old male with autosomal dominant dystrophic EB, presenting with bilateral leg swelling of one-week duration. There was no other significant past medical history. The physical examination was remarkable for scars and erosions over all body areas, with all extremities with blisters and ulcers covered, absent finger and toenails and bilateral lower extremity edema. Serum creatinine was 0.9 mg/dL, albumin 1.3 g/dL and urine protein excretion 3.7 g/24 h. Viral markers (hepatitis-B, C, and HIV), complement c3 and c4 levels and auto-immune antibody profile all remained negative or within normal limits. Renal ultrasound and echocardiogram were normal. Renal biopsy recovered 14 glomeruli, all with proliferation of mesangial and endothelial cells as well as an expansion of the mesangial matrix, focal segmental sclerosis and amorphous homogeneous deposits demonstrating apple-green birefringence under polarized light with Congo red stain. Our observation emphasizes the importance of recognizing MPGN and secondary amyloidosis in patients with EB, especially with the availability of newer treatment modalities.

A multicentre investigation of organ and tissue donation education for critical care residents.

PURPOSE: To describe critical care medicine residents' training, expertise, and skills regarding organ and tissue donation processes and procedures. METHODS: We undertook a qualitative multicentre study and employed a purposive sample of program directors, physicians, nurses, residents, and organ donation leaders from all nine academic intensive care unit (ICU) training centres (five adult, four pediatric) in Ontario (n = 71). Interviews, conducted by telephone between December 2015 and March 2016, were audio-recorded and transcribed verbatim. Data collection and analysis were performed using an iterative process and continued until saturation was achieved. RESULTS: Five main themes were identified: 1) gaps in residents' knowledge for both neurologic determination of death (NDD) and circulatory determination of death (DCD) cases; 2) commitment to the provision of organ and tissue donation training; 3) limited experiential learning (NDD and DCD); 4) challenges related to the provision of training on organ donation and need for a standardized curriculum; and 5) communication with family members. Overall, this study showed system-level gaps in training resulting from the lack of a standardized provincial curriculum on organ donation. CONCLUSIONS: Qualitative data corroborated that residents need more exposure to clinical cases, especially regarding DCD donors. A standardized education curriculum would be beneficial for all residents within the ICU. Developing a better shared understanding of the donation process will improve team communication and performance, translate into a better end-of-life experience for families, and potentially result in increased donation rates.

Facteurs qui influent sur le consentement au don d'organes : étude rétrospective basée dans la population.

CONTEXTE: Améliorer l'approche des donneurs d'organes potentiels et obtenir leur consentement pourrait favoriser l'autonomie des patients et donner accès à un plus grand nombre d'organes à transplanter. Nous avons voulu identifier les facteurs modifiables qui influent sur le consentement au don d'organes. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective regroupant les adultes (≥ 18 ans) consécutivement orientés vers le système de don d'organes en Ontario entre avril 2013 et juin 2019. Nous avons analysé les données cliniques et démographiques des patients, les données relatives à leurs mandataires et les particularités des approches pour le consentement au don. Les paramètres de l'étude étaient le consentement au don d'organes et le taux d'approches. Nous avons analysé les liens indépendants entre le consentement et les facteurs propres aux approches et au système. RÉSULTATS: Nous avons identifié 34 837 signalements de donneurs d'organes potentiels, dont 6548 (18,8 %) ont fait l'objet d'approches auprès de leurs mandataires en vue d'un consentement. Parmi ces derniers, 3927 (60,0 % des approches) ont mené à un consentement au don d'organes et 1883 patients (48,0 % des consentements) ont effectivement été donneurs. La raison la plus courante pour laquelle des mandataires n'ont pas été approchés en vue du consentement à un don potentiel était un retard de signalement de la part de l'équipe soignante (45,2 %). Les facteurs modifiables indépendants associés au consentement incluaient : approche téléphonique (rapport des cotes [RC] ajusté 0,46, intervalle de confiance IC à 95 % 0,35­0,58) et approche en collaboration avec le médecin et la coordination des dons (RC ajusté 1,26, IC à 95 % 1,01­1,59). INTERPRÉTATION: Le consentement au don d'organes a été associé à plusieurs facteurs modifiables. Les organisations devraient cibler des interventions visant à assurer un signalement rapide aux organisations de don d'organes, favoriser les approches en personne et promouvoir la participation des médecins au processus d'approche.