Impact of Donation After Circulatory Death on Outcomes of Expanded Criteria Donor Kidney Transplants.

Expanded criteria donor (ECD) kidneys experience suboptimal outcomes compared with standard criteria donor kidneys. To examine the additional impact of deceased organ category, donation after circulatory death (DCD), and neurologic determination of death (NDD) on ECD outcomes, we examined 1- and 3-year patient and graft survival in all ECD kidney recipients in our institution between January 2008 and December 2017. Of 166 ECD recipients, 49 (29.5%) were DCD and 117 (70.5%) were NDD. Delayed graft function was higher in the DCD/ECD group 61.2 % vs 32.0 % among NDD/ECD recipients. Graft loss was significantly increased among DCD/ECD (hazard ratio for graft loss 4.81 [95% CI1.78-13.01], P = .002 at 1 year and 2.03 [95% CI 1.03-4.0], P = .042 at 3 years). Death-censored graft loss was higher among DCD/ECD (hazard ratio was 10.12 [95% CI, 2.14, 47.92], P = .004 at 1 year and 2.83 [95% CI, 1.24, 6.46], P = .014 at 3 years). There was no statistically significant difference in all-cause mortality. Our study demonstrated that DCD/ECD kidneys have lower graft survival compared with NDD/ECD kidneys. Time on dialysis, waiting time, and panel reactive antibody should be taken into account when offering these organs to patients.

Risk and Timing of Major Bleeding Complications Requiring Intervention of the Percutaneous Kidney Biopsy With a Short Observation Protocol: A Retrospective Chart Review.

Background: We previously published a retrospective study of kidney biopsies performed in a tertiary care hospital in London, Ontario from 2012 to 2017. This study resulted in a change of practice in our institution to shorter postbiopsy monitoring for outpatients as well as the development of a risk calculator to predict serious bleeding complications. Objective: The primary objective of this study was to determine whether this shorter monitoring time is adequate in the outpatient setting. A secondary objective was to validate the bleeding risk calculator in both inpatients and outpatients. Design: This was a retrospective chart review. Setting: This study was performed at a tertiary academic hospital in London, Ontario, Canada. Participants: This was a retrospective study of 400 adult patients who underwent kidney biopsy between April 30, 2018 and February 25, 2022 at a tertiary academic hospital in London, Canada. Methods: We retrospectively assessed frequency and timing of major bleeding complications in patients who underwent kidney biopsy. In secondary analyses, we examined the prediction performance of the risk calculator in discrimination and calibration. Results: Major bleeding occurred in 7 patients (1.8%). Five of these patients required blood transfusions (1.3%) and 2 required embolization (0.5%). In the outpatient setting, any major bleeding events were identified immediately (1 patient) or on the routine 2-hour ultrasounds (1 patient). The risk calculator showed good discrimination (C-statistic, 0.91, 95% confidence interval [CI] = [0.84 to 0.95]) and calibration (slope, 1.10, 95% CI = [0.47 to 1.74]; intercept, 95% CI = -0.02 [-0.79 to 0.75]), but with much uncertainty in the estimates. Limitations: The occurrence of only a few major bleeding events limits the reliability of our assessment of our risk calculator. Conclusions: There appears to be little yield in extending observation beyond 2 hours after an outpatient kidney biopsy with the use of immediate and 2-hour postbiopsy ultrasounds. The bleeding risk calculator (http://perioperativerisk.com/kbrc) warrants further validation.

Contexte: Nous avons publié précédemment une étude rétrospective des biopsies rénales effectuées entre 2012 et 2017 dans un hôpital de soins tertiaires de London, en Ontario. Les résultats de cette précédente étude ont entraîné un changement de pratique dans notre établissement, soit une réduction de la durée de la surveillance post-biopsie pour les patients ambulatoires, et la mise au point d'un calculateur de risque permettant de prédire les complications hémorragiques graves. Objectifs: L'objectif principal de l'étude en cours était de vérifier si ce temps de surveillance plus court est adéquat pour les patients ambulatoires. Un deuxième objectif était de valider le calculateur de risque d'hémorragie chez les patients hospitalisés et les patients ambulatoires. Conception: Étude rétrospective des dossiers médicaux. Cadre: Étude réalisée dans un hôpital de soins tertiaires de London, en Ontario (Canada). Sujets: Cette étude rétrospective portait sur 400 patients adultes ayant subi une biopsie rénale entre le 30 avril 2018 et le 25 février 2022 dans un centre hospitalier universitaire de soins tertiaires de London, au Canada. Méthodes: Nous avons procédé à un examen rétrospectif de la fréquence des complications hémorragiques graves, et du moment où celles-ci surviennent, chez les patients ayant subi une biopsie rénale. Dans les analyses secondaires, nous avons examiné la puissance prédictive du calculateur de risque en matière de discrimination et d'étalonnage. Résultats: Sept patients (1,75 %) ont subi une hémorragie majeure; de ces patients, cinq ont eu besoin de transfusions sanguines (1,3 %) et deux, d'une embolisation (0,5 %). En contexte ambulatoire, tous les événements hémorragiques graves ont été détectés immédiatement (un patient) ou lors de l'échographie de routine à deux heures (un patient). Le calculateur de risque a montré une bonne discrimination (statistique C : 0,91 [IC 95 % : 0,84 à 0,95]) et un bon étalonnage (pente : 1,10 [0,47 à 1,74]; point d'intersection : -0,02 [-0,79 à 0,75]), mais une grande incertitude dans les estimations. Limitations: La fiabilité de l'évaluation de notre calculateur de risque est limitée par le très faible échantillon d'événements hémorragiques graves étant survenus. Conclusion: Il semble y avoir peu d'intérêt à prolonger la surveillance au-delà de deux heures après une biopsie rénale chez les patients ambulatoires lorsqu'une échographie est pratiquée immédiatement après la procédure et deux heures plus tard. Le calculateur de risque d'hémorragie (http://perioperativerisk.com/kbrc) nécessite une validation plus approfondie.

Microscopic Kidney Disease in Tuberous Sclerosis Complex and Treatment With mTOR Inhibition.

Declining kidney function in tuberous sclerosis complex (TSC) is often attributed to large lesions, including angiomyolipomas (AMLs) and cysts, that encroach on the normal parenchyma or that require intervention and loss of parenchyma from surgical debulking or embolization. Consequently, research on inhibitors of the mammalian target of rapamycin (mTOR), a protein complex implicated in TSC pathophysiology for its role in promoting cell growth and proliferation, has largely focused on their ability to reduce AML size. Clinical guidelines distilled from this research limit mTOR inhibition as a first-line treatment to patients with large AMLs. However, chronic kidney disease (CKD) occurs in patients without large AMLs or a history of renal intervention. Alternate mechanisms postulated for CKD in TSC may suggest a role for mTOR inhibition in this population. In this report, we present 2 cases of a microscopic variant of TSC kidney disease causing declining kidney function, as well as anecdotal evidence for the use of mTOR inhibition to improve kidney function in the absence of large AMLs. We highlight the importance of annual kidney function assessment in patients with TSC and suggest a low threshold for kidney biopsy in patients with declining glomerular filtration rate without a clear etiology clinically or radiographically.

Epidemiology and Outcomes of AKI Treated With Continuous Kidney Replacement Therapy: The Multicenter CRRTnet Study.

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery. Study Design: Multicenter, prospective living registry. Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded. Exposure: CKRT for more than 24 hours. Outcomes: Hospital mortality, kidney recovery, and health care resource utilization. Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively. Results: Patients' characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P < 0.001), had greater comorbidity (median Charlson score 3 [1-4] vs. 2 [1-3], P < 0.001), and higher acuity of illness (median APACHE-II score 30 [25-35] vs. 29 [24-33], P = 0.003). The most common condition predisposing to AKI was sepsis (42.6%), and the most common CKRT indications were oliguria/anuria (56.2%) and fluid overload (53.9%). Standardized mortality ratios were similar among centers. Limitations: The generalizability of these results to CKRT practices in nonacademic centers or low-and middle-income countries is limited. Conclusions: In this registry, sepsis was the major contributor to AKI and fluid management was collectively the most common CKRT indication. Significant heterogeneity in patient- and CKRT-specific characteristics was found in current practice. These data highlight the need for establishing benchmarks of CKRT delivery, performance, and patient outcomes. Data from this registry could assist with the design of such studies.

Investigation of N,N,N-Trimethyl-L-alanyl-L-proline Betaine (TMAP) as a Biomarker of Kidney Function.

Glomerular filtration rate (GFR) is the most widely used tool for the measurement of kidney function, but endogenous biomarkers such as cystatin C and creatinine have limitations. A previous metabolomic study revealed N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP) to be reflective of kidney function. In this study, we developed a quantitative LCMS assay for the measurement of TMAP and evaluated TMAP as a biomarker of GFR. An assay to measure TMAP was developed using liquid chromatography-mass spectrometry. After validation of the method, we applied it to plasma samples from three distinct kidney disease patient cohorts: nondialysis chronic kidney disease (CKD) patients, patients receiving peritoneal and hemodialysis, and living kidney donors. We investigated whether TMAP was conserved in other mammalian and nonmammalian species, by analyzing plasma samples from Wistar rats with diet-induced CKD and searching for putative matches to the m/z for TMAP and its known fragments in the raw sample data repository "Metabolomics Workbench". The assay can measure plasma TMAP at a lower limit of quantitation (100 ng/mL) with an interday precision and accuracy of 12.8 and 12.1%, respectively. In all three patient cohorts, TMAP concentrations are significantly higher in patients with CKD than in controls with a normal GFR. Further, TMAP concentrations are also elevated in rats with CKD and TMAP is present in the sap produced from Acer saccharum trees. TMAP concentration is inversely related to GFR suggesting that it is a marker of kidney function. TMAP is present in nonmammalian species suggesting that it is part of a biologically conserved process.

The effect of late-onset CMV infection on the outcome of renal allograft considering initial graft function.

BACKGROUND: Delayed graft function (DGF) increases the renal allograft failure risk. Late-onset Cytomegalovirus (CMV) infection's effect on the association between DGF and allograft failure has not been determined. METHODS: In this retrospective cohort, we included all renal allograft recipients at London Health Sciences Centre from January 1, 2014 to December 30, 2017, and continued clinical follow-up until February 28, 2020. We determined whether late-onset CMV infection affects the association between DGF and allograft failure in stratified and Cox proportional hazard analyses. RESULTS: Of 384 patients (median age [interquartile range]: 55 [43.3-63]; 38.7% female), 57 recipients (14.8%) were diagnosed with DGF. Patients with DGF were at a greater risk of CMV infection than patients without DGF (22.8% vs. 11.3%, p = .017). Late-onset CMV infection (odds ratio [OR]: 4.7, 95% CI: 2.07-10.68) and rejection (OR: 9.59, 95% CI: 4.15-22.16) significantly increased the risk of allograft failure in recipients with DGF. Patients with DGF had a significantly greater risk of graft failure than those without DGF (17.5% vs. 6.1%, p = .007). In the adjusted Cox hazard model, CMV infection significantly increased the risk of allograft failure (aHR: 3.19, 95% CI: 1.49-6.84). CONCLUSION: Late-onset CMV infection considerably increased the risk of graft failure in patients with DGF. A hybrid preventive model including prophylaxis followed by CMV-specific cell-mediated immunity monitoring may decrease the risk of allograft failure in recipients with DGF.

The Renal Community Photo Initiative: A Program Report in Ontario, Canada.

Purpose of Program: We initiated the Renal Community Photo Initiative to better understand why some hemodialysis users express significant capacities for resilience and hope, demonstrating outward-looking perspectives and enjoying a rich quality of life. Sources of Information: "Photovoice" is a participatory research methodology that encourages individuals to develop positive self-perceptions with photography. Photovoice empowers participants as informants within their communities. Visual arts researchers surveyed existing Photovoice studies to identify gaps in knowledge to be addressed in this study, including challenges related to fostering participant agency and social action. Images and logs were collected and reviewed during organized, participant-led substudy groups. These meetings provided researchers with core study values and direction as to how the images and additional information should be used to raise awareness about living with chronic kidney disease. Methods: To address the complexity of the human condition, the Renal Community Photo Initiative offered participants an array of diverse and accessible image-making techniques. No narrative directives for image-making were provided. This qualitative, interdisciplinary, participant-centric study invited adult chronic hemodialysis patients in 4 dialysis units in London and Stratford, Ontario, to participate. The research team designed a selection of different, accessible photo technologies for participant use. Eligible participants were invited to select photographic technologies and given the additional option to write accompanying logs. Researchers organized substudy meetings for participant-led focus groups to discuss core study values and personal encounters with images and image-making. Participants directed how their generated images should be shared with the public and researchers. Key Findings: A total of 40 participants have been recruited to date, producing more than 1600 images and an archive of handwritten logs. Three participant-led focus groups have established priorities for image sharing and a core set of values for subsequent study phases. A series of public presentations of participant images took place. The research team will pursue further public presentation opportunities and the development of a suitable research database. Limitations: Organizing and categorizing images for access in an interdisciplinary research database remains a challenge. Current health and safety protocols related to COVID-19 require the study to pause recruitment and substudy meetings and reassess immediate outputs for visuals. Implications: A qualitative study of this scope offers a new model for participant agency and collaboration. It requires the onboarding of interdisciplinary researchers to effectively engage with its significant image and log archive. Participants should remain involved in directing future steps for disseminating their images. Following substudy directives, researchers are developing visuals for health care and public settings, and determining opportunities for participants to share their experience in both clinic- and public-based settings.

Objectif du programme: Nous avons lancé la Renal Community Photo Initiative afin de mieux comprendre pourquoi certains utilisateurs de l'hémodialyse font preuve d'importantes capacités de résilience et d'espoir, sont tournés vers le monde extérieur et jouissent d'une riche qualité de vie. Sources: « Photovoice ¼ est une méthodologie de recherche participative qui encourage les individus à développer une perception de soi positive grâce à la photographie. Photovoice permet aux participants de devenir des informateurs au sein de leurs communautés. Les chercheurs en arts visuels ont mené une enquête sur les études existantes de Photovoice afin de révéler les lacunes dans les connaissances qui pourraient être comblées par la présente étude, notamment les défis liés à la promotion de la participation et de l'action sociale des participants. Des images et des registres ont été recueillis et examinés lors de sous-groupes d'étude organisés et dirigés par les participants par les participants. Ces réunions ont permis aux chercheurs de définir les valeurs fondamentales de l'étude et d'indiquer comment utiliser les images et les autres informations pour sensibiliser les gens à la vie avec maladie rénale chronique. Méthodologie: Afin d'aborder la complexité de la condition humaine, la Renal Community Photo Initiative a offert aux participants une gamme diverse et accessible de techniques de création d'images. Aucune directive narrative n'a été fournie pour la création des images. Cette étude qualitative, interdisciplinaire et axée sur les participants a invité des adultes suivant des traitements d'hémodialyse chronique dans quatre unités de dialyse de London et Stratford (Ontario) à participer. L'équipe de recherche a conçu une sélection de technologies photographiques diverses et accessibles à l'usage des participants. Les participants admissibles ont été invités à choisir des technologies photographiques et à tenir un journal s'ils le souhaitaient. Les chercheurs ont organisé des réunions de sous-étude pour des groupes de discussion dirigés par les participants afin de discuter des valeurs fondamentales de l'étude et des expériences personnelles avec les images et la création d'images. Les participants ont établi la façon dont leurs images devraient être partagées avec le public et les chercheurs. Principaux résultats: À ce jour, 40 participants ont été recrutés et plus de 1 600 images ont été produites, de même qu'une archive de journaux manuscrits. Trois groupes de discussion dirigés par les participants ont établi les priorités pour le partage des images ainsi qu'un ensemble de valeurs fondamentales en vue des phases ultérieures de l'étude. Plusieurs présentations publiques des images des participants ont eu lieu. L'équipe de recherche poursuivra les présentations publiques et l'élaboration d'une base de données de recherche. Limites: L'organisation et la catégorisation des images pour y accéder dans une base de données de recherche interdisciplinaire demeurent un défi. Les protocoles actuels de santé et de sécurité liés à la COVID-19 empêchent le recrutement et les réunions de sous-étude pour le moment et imposent de réévaluer les résultats immédiats pour les visuels. Conclusion: Une étude qualitative de cette envergure offre un nouveau modèle pour la participation et collaboration des patients. Elle exige l'intégration de chercheurs interdisciplinaires afin d'exploiter efficacement ses importantes archives d'images et de journaux. Il importe que les participants demeurent impliqués dans la direction des prochaines étapes de diffusion de leurs images. Suivant les directives de la sous-étude, les chercheurs développent des visuels pour les soins de santé et les milieux publics, et recensent les occasions pour les participants de partager leur expérience tant dans les milieux cliniques que publics.

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.

Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys.

Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups (r2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 (P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Laustsen and Bøgh in this issue.

Adults with tuberous sclerosis complex: A distinct patient population.

OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.

Potential Pitfalls in Pre-implantation Genetic Diagnosis in a Patient with Tuberous Sclerosis and Isolated Mosaicism for a TSC2 Variant in Renal Tissue.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that displays a wide spectrum of clinical manifestations, often affecting multiple organs including the kidneys, brain, lungs, and skin. A pathogenic mutation in either the TSC1 or TSC2 gene can be detected in almost 85% of the cases, with mosaicism accounting for about half of the remaining cases. We report a case of TSC diagnosed clinically, requesting genetic counselling regarding reproductive risks. No mutation was identified on initial testing of peripheral blood; however, mosaicism for a likely pathogenic frameshift variant in TSC2 was detected at a level of 15% in renal angiomyolipoma tissue. Despite widespread clinical manifestations of TCS, this variant was not detected in skin fibroblasts or saliva, raising the possibility this is an isolated somatic mutation in renal tissue with the underlying germline mutation not yet identified. This case highlights the difficulties when counselling patients with mosaicism regarding their reproductive risks and prenatal diagnostic options.

COVID-19 chez les patients ontariens sous dialyse à long terme.

CONTEXTE: Les patients sous dialyse à long terme pourraient avoir un risque accru d'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), et de maladie et de mortalité associées. Nous avons voulu décrire l'incidence, les facteurs de risque et les issues de l'infection chez ces patients en Ontario (Canada). MÉTHODES: Nous avons utilisé des ensembles de données reliées pour comparer les caractéristiques de la maladie et la mortalité chez les patients sous dialyse à long terme en Ontario qui ont testé positif pour le SRAS-CoV-2 et ceux qui n'ont pas développé d'infection, entre le 12 mars et le 20 août 2020. Nous avons recueilli des données sur l'infection par le SRAS-CoV-2 de manière prospective. Nous avons évalué les facteurs de risque d'infection et de mortalité par des analyses de régression logistique multivariées. RÉSULTATS: Pendant la période à l'étude, 187 patients dialysés sur 12 501 (1,5 %) ont reçu un diagnostic d'infection par le SRAS-CoV-2. Parmi eux, 117 (62,6 %) ont été hospitalisés, et le taux de mortalité était de 28,3 %. Les facteurs prédictifs significatifs associés à l'infection incluaient l'hémodialyse dans un centre plutôt que la dialyse à domicile (rapport de cotes [RC] 2,54; intervalle de confiance [IC] à 95 % 1,59­4,05), le fait de vivre dans un établissement de soins de longue durée (RC 7,67; IC à 95 % 5,30­11,11), le fait d'habiter la région du Grand Toronto (RC 3,27; IC à 95 % 2,21­4,80), les ethnicités Noire (RC 3,05; IC à 95 % 1,95­4,77), du sous-continent indien (RC 1,70; IC à 95 % 1,02­2,81) et autres non blanches (RC 2,03; IC à 95 % 1,38­2,97) et les quintiles de revenu inférieurs (RC 1,82; IC à 95 % 1,15­2,89). INTERPRÉTATION: Les patients sous dialyse à long terme sont exposés à un risque accru d'infection par le SRAS-CoV-2 et de mortalité due à la maladie à coronavirus 2019. Il faudra travailler à éliminer les facteurs de risque d'infection et vacciner ces patients en priorité.

Autoantibodies to LG3 are associated with poor long-term survival after liver retransplantation.

Autoantibodies are detrimental to the survival of organ transplantation. We demonstrated that Angiotensin II Type I Receptor agonistic autoantibodies (AT1R-AA) were associated with poor outcomes after liver retransplantation. To examine the effect of other autoantibodies, we studied a retrospective cohort of 93 patients who received a second liver transplant. Pre-retransplant sera were tested with Luminex-based solid-phase assays. Among 33 tested autoantibodies, 15 were significantly higher in 48 patients who lost their regrafts than 45 patients whose regrafts were still functioning. Specifically, patients with autoantibodies to the C-terminal laminin-like globular domain of Perlecan (LG3) experienced significantly worse regraft survival (p = .002) than those with negative LG3 autoantibodies (LG3-A). In multivariate analysis, LG3-A (HR = 2.35 [1.11-4.98], p = .027) and AT1R-AA (HR = 2.09 [1.07-4.10], p = .032) remained significant predictors of regraft loss after adjusting for recipient age and sex. There were synergistic deleterious effects on regraft survival in patients who were double-positive for LG3-A and donor-specific antibody (DSA) (HR = 5.26 [2.15-12.88], p = .001), or LG3-A and AT1R-AA (HR = 3.23 [1.37-7.66], p = .008). All six double-positive patients lost their liver regrafts. In conclusion, LG3-A is associated with inferior long-term outcomes of a second liver transplant. Screening anti-HLA antibodies and autoantibodies such as LG3-A/AT1R-AA identifies patients with a higher risk for liver transplantation.

Late-onset allograft rejection, cytomegalovirus infection, and renal allograft loss: Is anti-CMV prophylaxis required following late-onset allograft rejection?

Renal transplant recipients remain at risk of delayed-onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early-vs late-onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long-term allograft outcome. Median (IQR) duration of follow-up was 1186.0 (904.7-1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R- CMV serostatus (OR: 5.5, 95% CI: 2.5-12.2) and LAR (OR: 7.9, 95% CI: 2.8-22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed-onset CMV infection (HR: 2.51, 95% CI: 1.08-5.86) and LAR (HR: 5.46, 95% CI: 2.26-13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late-onset CMV infection. Post-LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.

COVID-19 in patients undergoing long-term dialysis in Ontario.

BACKGROUND: Patients undergoing long-term dialysis may be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of associated disease and mortality. We aimed to describe the incidence, risk factors and outcomes for infection in these patients in Ontario, Canada. METHODS: We used linked data sets to compare disease characteristics and mortality between patients receiving long-term dialysis in Ontario who were diagnosed SARS-CoV-2 positive and those who did not acquire SARS-CoV-2 infection, between Mar. 12 and Aug. 20, 2020. We collected data on SARS-CoV-2 infection prospectively. We evaluated risk factors for infection and death using multivariable logistic regression analyses. RESULTS: During the study period, 187 (1.5%) of 12 501 patients undergoing dialysis were diagnosed with SARS-CoV-2 infection. Of those with SARS-CoV-2 infection, 117 (62.6%) were admitted to hospital and the case fatality rate was 28.3%. Significant predictors of infection included in-centre hemodialysis versus home dialysis (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.59-4.05), living in a long-term care residence (OR 7.67, 95% CI 5.30-11.11), living in the Greater Toronto Area (OR 3.27, 95% CI 2.21-4.80), Black ethnicity (OR 3.05, 95% CI 1.95-4.77), Indian subcontinent ethnicity (OR 1.70, 95% CI 1.02-2.81), other non-White ethnicities (OR 2.03, 95% CI 1.38-2.97) and lower income quintiles (OR 1.82, 95% CI 1.15-2.89). INTERPRETATION: Patients undergoing long-term dialysis are at increased risk of SARS-CoV-2 infection and death from coronavirus disease 2019. Special attention should be paid to addressing risk factors for infection, and these patients should be prioritized for vaccination.

Long-lasting cluster of nosocomial pneumonia with a single Pneumocystis jirovecii genotype involving different organ allograft recipients.

Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non-SOT patients. Post-transplant PCP was frequently an acute-onset disease (90% vs. 18.2%, p = .01) requiring ICU admission (70% vs. 20%, p = .03) and hemodialysis (60% vs. 0, p = .003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p = .36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non-SOT patients. Reinstitution of prophylaxis successfully controlled post-transplant cluster until end of observation period in October 2019. No transmission was detected from non-SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required.

The effect of human leukocyte antigen A1 and B35-Cw4 on sustained BK polyomavirus DNAemia after renal transplantation.

Human leukocyte antigen (HLA) class I presentation pathway plays a central role in natural killer (NK) cell and cytotoxic T-cell activities against BK polyomavirus (BKPyV) DNAemia. We determined the risk of sustained BKPyV DNAemia in 175 consecutive renal transplant recipients considering the simultaneous effect of donor/recipient HLA class I antigens and pre- or post-transplant variables. Median (IQR) age was 53 (44-64) years, and 37% of patients were female. 40 patients (22.9%) developed sustained BKPyV DNAemia [median (IQR) viral load: 9740 (4350-17 125) copies/ml]. In the Cox proportional hazard analysis, HLA-A1 (HR: 3.06, 95% CI: 1.51-6.17) and HLA-B35-Cw4 (HR: 4.63, 95% CI: 2.12-10.14) significantly increased the risk of sustained BKPyV DNAemia, while 2 HLA-C mismatches provided a marginally protective effect (HR: 0.32, 95% CI: 0.10-0.98). HLA-Cw4 is a ligand for NK cell inhibitory receptor, and HLA-B35 is in strong linkage disequilibrium with the HLA-Cw4 allele. The association between HLA-B35-Cw4 expression and sustained BKPyV DNAemia supports the important role of cytotoxic T cells and NK cells that would normally control BKPyV activation through engagement with immunoglobulin-like killer receptors (KIRs). Further studies are required to investigate the effect of HLA-C alleles along with NK cell activity against BKPyV DNAemia.

Starch or Saline After Cardiac Surgery: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Despite decades of investigation, the balance of clinical risks and benefits of fluid supplementation with starch remain unresolved. Patient-centered outcomes have not been well explored in a "real-world" trial in cardiac surgery. OBJECTIVE: We sought to compare a starch-based fluid strategy with a saline-based fluid strategy in the cardiac surgery patient. DESIGN: A pragmatic blinded randomized controlled trial comparing starch-based with saline-based fluid strategy. SETTING: A large tertiary academic center in London Ontario between September 2009 and February 2011. PARTICIPANTS: Patients undergoing planned, isolated coronary revascularization. MEASUREMENTS: Serum creatinine and patient weight were measured daily postoperatively. METHODS: Patients were randomized to receive 6% hydroxyethyl starch (Voluven) or saline for perioperative fluid requirements. Fluid administration was not protocolized. Co-primary outcomes were incidence of acute kidney injury (AKI) and maximum postoperative weight gain. Secondary outcomes included bleeding, transfusion, inotropic and ventilator support, and fluid utilization. RESULTS: The study was prematurely terminated due to resource limitations. A total of 69 patients (19% female, mean age = 65) were randomized. Using RIFLE criteria for AKI, "risk" occurred in 12 patients in each group (risk ratio [RR] = 1.0; 95% confidence interval [CI] = 0.5-1.9; P = 1.00), whereas "injury" occurred in 7 of 35 (20%) and 3 of 34 (9%) of patients in the starch and saline groups, respectively (RR = 2.3; 95% CI = 0.6-8.1; P = .31). Maximum weight gain, bleeding and blood product usage, and overall fluid requirement were similar between groups. LIMITATIONS: The study had to be prematurely terminated due to resource limitations which led to a small sample size which was not sufficiently powered to detect a difference in the primary outcomes. CONCLUSIONS: This pragmatic double-blinded randomized controlled trial revealed a number of interesting hypothesis-generating trends and confirmed the feasibility of undertaking a logistically complex trial in a pragmatic fashion.

CONTEXTE: L'équilibre entre les avantages et les risques cliniques d'une supplémentation en fluides à base d'amidon n'est toujours pas établi malgré des décennies d'études. Les résultats des patients subissant une chirurgie cardiaque n'ont pas été explorés suffisamment dans le cadre d'un essai concret. OBJECTIF: Comparer deux stratégies de supplémentation liquidienne, une solution à base d'amidon et une solution saline, chez des patients subissant une chirurgie cardiaque. TYPE D'ÉTUDE: Un essai pragmatique, contrôlé, à répartition aléatoire et mené en double insu comparant deux stratégies de supplémentation liquidienne une solution à base d'amidon et une solution saline. CADRE: Un grand centre universitaire de soins tertiaires de London (Ontario) entre septembre 2009 et février 2011. SUJETS: Des patients subissant une revascularisation coronarienne planifiée et isolée. MESURES: La créatinine sérique et le poids du patient ont été mesurés quotidiennement à la suite de l'intervention. MÉTHODOLOGIE: Les patients ont été répartis aléatoirement pour recevoir du Voluven (solution d'amidon hydroxyéthylé à 6 %) ou une solution saline pour les fluidiques périopératoires. L'administration ne s'est pas faite selon un protocole établi. L'incidence d'insuffisance rénale aiguë (IRA) et un gain pondéral maximal après l'intervention constituaient les deux principaux résultats mesurés. Les résultats secondaires incluaient une hémorragie, l'utilisation de transfusion sanguine, d'inotrope, d'assistance respiratoire et l'administration de fluides. RÉSULTATS: L'étude a été interrompue prématurément par manque de ressources. Les 69 patients (19 % de femmes) répartis aléatoirement avaient en moyenne 65 ans. La classification RIFLE avait permis de détecter un « risque ¼ d'IRA chez 12 patients dans chacun des groupes (RC: 1,0; IC 95 %: 0,5-1,9; p=1,00) et une « insuffisance ¼ chez 7 patients sur 35 (20 %) du groupe « amidon ¼ et 3 patients sur 34 (9 %) du groupe « saline ¼ (RC: 2,3; IC 95 %: 0,6-8,1; p=0,31). Le gain pondéral maximal, le nombre d'hémorragies, l'utilisation de produits sanguins et les besoins liquidiens étaient similaires dans les deux groupes. LIMITES: L'étude a été interrompue prématurément en raison d'un manque de ressources. Par conséquent, le faible échantillon de patients s'avère insuffisamment puissant pour détecter des différences significatives entre les deux groupes. CONCLUSIONS: Cette étude a mis en lumière quelques tendances permettant d'émettre des hypothèses intéressantes. L'étude a également confirmé la possibilité d'entreprendre un essai logistique complexe de manière pragmatique.