Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol.

Background: Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective: This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design: A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting: Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants: Adult participants with G3-G5 CKD and metabolic acidosis. Measurements: Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods: A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations: Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions: This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration: This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) courent le risque de développer une acidose métabolique, laquelle est associée à une progression plus rapide de l'IRC et à un besoin accru de dialyse. La prise de bicarbonate de sodium par voie orale (la norme actuelle de traitement de l'acidose métabolique) est mal tolérée, ce qui se traduit par une faible adhérence. Les fruit et légumes basiques ou alcalifiants ont un potentiel de traitement alternatif pour l'acidose métabolique, car il a été démontré qu'ils peuvent réduire la charge acide provenant de l'alimentation. Objectif: cet essai permettra d'évaluer la faisabilité d'un traitement alimentaire de l'acidose métabolique, en misant sur la consommation de fruit et légumes basiques ou alcalifiants, par rapport à la prise de bicarbonate de sodium par voie orale. Type d'étude: essai de faisabilité contrôlé, randomisé, ouvert, à deux bras, mené dans deux centres. Cadre: deux sites canadiens, soit une clinique de néphrologie à Winnipeg (Manitoba) et une autre à Halifax (Nouvelle-Écosse). Sujets: des patients adultes atteints d'IRC de stade G3-G5 et d'acidose métabolique. Mesures: les participants seront soumis à des mesures initiales et devront se présenter à cinq visites d'étude réparties sur 12 mois. Au cours de chacune, les patients subiront une mesure des critères de faisabilité, une mesure de la pression artérielle, un bilan sanguin et urinaire, un test de lever de chaise à cinq répétitions (STS5 ­ Five Times Sit to Stand Test) et devront répondre à des questionnaires évaluant la qualité de vie et les symptômes. Les participants devront également utiliser un outil en ligne de rappels alimentaires de 24 heures autoadministrés et automatisés (ASA24 ­ Automated Self-Administered 24-hours) au début, à mi-parcours et à la fin de l'essai. Méthodologie: 40 patients admissibles seront randomisés (1:1) dans le groupe expérimental (fruit et légumes basiques ou alcalifiants) ou dans le groupe témoin (bicarbonate de sodium) avec une dose quotidienne initiale de 1 500 mg. Limites: l'utilisation d'outils d'évaluation alimentaire autoadministrés, le manque de supervision de la consommation des traitements à l'étude et la possible déception du groupe témoin de ne pas recevoir de fruit et légumes constituent des limites pour cette étude. Nous prévoyons cependant adopter des pratiques appropriées pour surmonter ces possibles limites. Ces pratiques sont discutées plus en détail dans le manuscrit. Conclusion: cette étude produira des données sur la consommation de fruit et légumes basiques ou alcalifiants comme traitement alimentaire pour l'acidose métabolique en contexte d'IRC. Ces données seront utilisées pour concevoir un futur essai multicentrique visant à ralentir la progression de l'IRC chez les personnes atteintes d'acidose métabolique. Enregistrement de l'essai: Cette étude a reçu l'approbation du Conseil d'éthique de la recherche en santé de l'Université du Manitoba (HS24768 [B2021:025]) et est enregistrée sur ClinicalTrials.gov avec l'identifiant NCT05113641.

Patient and Provider Gender and Kidney Transplant Referral in Canada: A Survey of Canadian Healthcare Providers.

BACKGROUND: Referral for kidney transplant (KT) is variable, with women often disadvantaged. This study aimed to better characterize Canadian transplant referral practices and identify potential differences by respondent and/or patient gender using surveys targeted at healthcare practitioners (HCPs) involved in KT. METHODS: Surveys consisting of 25 complex patient cases representing 7 themes were distributed to KT HCPs across Canada (March 3, 2022-April 27, 2022) using national nephrology/transplant society email registries. Respondents were asked whether they would refer the patient for transplant. Two identical surveys were created, differing only by gender/gender pronouns used in each case. Multivariable logistic regression was used to assess the association of respondent demographics and patient themes (including case gender) with the odds of transplant referral (overall and stratifying by respondent gender). RESULTS: Overall, the referral rate was 58.0% among 97 survey respondents (46.4% male). Case themes associated with a lower likelihood of referral included adherence concerns (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.45-0.94), medical complexity (aOR 0.57; 95% CI, 0.38-0.85), and perceived frailty (aOR 0.63; 95% CI, 0.47-0.84). Respondent gender was not associated with differences in KT referral (aOR 0.91; 95% CI, 0.65-1.26 for male versus female respondents) but modified the association of frailty (less referral for male than female respondents, P = 0.005) and medical complexity (less referral for female than male respondents, P = 0.009) with referral. There were no differences in referral rate by case gender ( P = 0.82). CONCLUSIONS: KT referral practices vary among Canadian HCPs. In this study, there were no differences in likelihood of transplant referral by candidate gender.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

Contexte: La période prolongée d'ischémie à chaud (WIT­warm ischemia time) et la période prolongée d'ischémie à froid (CIT­cold ischemia time) ont été associées de façon indépendante à une défaillance du greffon post-transplantation, mais leur effet combiné n'a jamais été étudié. Nous avons examiné l'effet combiné WIT/CIT sur la défaillance du greffon toutes causes confondues après une transplantation rénale. Méthodologie: Le Scientific Registry of Transplant Recipients a été utilisé pour identifier les receveurs d'une greffe de rein entre janvier 2000 et mars 2015 (date après laquelle la WIT n'a plus été rapportée séparément). Les patients ont été suivis jusqu'en septembre 2017. Une variable combinée WIT/CIT (excluant les valeurs extrêmes) a été dérivée de façon isolée pour les donneurs vivants et les donneurs décédés à l'aide d'une fonction spline cubique. La WIT du groupe référence pour les donneurs vivants se situait entre 10 et <23 minutes, et la CIT entre 0 et <0,42 heure; pour les donneurs décédés, la WIT se situait entre 10 et <25 minutes, et la CIT entre 1 et <7,75 heures. L'association corrigée entre une combinaison WIT/CIT et la défaillance du greffon toutes causes confondues (y compris le décès) a été analysée à l'aide de la régression de Cox. Les résultats secondaires incluaient une reprise retardée de la fonction du greffon (RRFG). Résultats: Un total de 137 125 receveurs d'un rein a été inclus. Dans le groupe des receveurs d'un organe provenant d'un donneur vivant, les patients avec une WIT/CIT prolongée (60 à ≤120 minutes/3,04 à ≤24 heures) présentaient un risque relatif corrigé plus élevé de défaillance du greffon (RRc: 1,61; IC 95 %: 1,14-2,29) par rapport au groupe de référence. Dans le groupe des receveurs d'un organe provenant d'un donneur décédé, une combinaison WIT/CIT de 63 à ≤120 minutes/28 à ≤48 heures a été associée à un RRc de 1,35 (IC 95 %: 1,16-1,58). La WIT/CIT prolongée a également été associée à une RRFG pour les deux groupes, bien que cet effet ait été davantage influencé par la CIT. Conclusion: La combinaison WIT/CIT est associée à la perte du greffon après la transplantation. Sachant qu'il s'agit de variables distinctes avec des déterminants différents, nous soulignons l'importance de rapporter la WIT et la CIT de façon indépendante. Qui plus est, les efforts visant à réduire la WIT et la CIT devraient être prioritaires.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

BACKGROUND AND PURPOSE: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. EXPERIMENTAL APPROACH: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. KEY RESULTS: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α-smooth muscle actin (α-SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin-angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty-six GPCRs were up-regulated in single Tcf21+ kidney fibroblasts, the most up-regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up-regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α-SMA+ interstitial cells in human kidney samples. CONCLUSION AND IMPLICATIONS: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.

Home dialysis in older adults: challenges and solutions.

There is a rising demand for dialysis in the older population given the increased numbers of older adults living with chronic kidney disease (CKD) progressing to kidney failure. Home dialysis, i.e. peritoneal dialysis (PD) and home hemodialysis (HHD), has been available for decades, but more recently there has been a rapid increase in home dialysis utilization as patients and clinicians consider its practical and clinical advantages. For older adults, incident home dialysis utilization more than doubled and prevalent home dialysis growth nearly doubled over the past decade. Whilst its advantages and recent rise in popularity are evident, there are numerous barriers and challenges that are important to consider prior to initiating older adults on home dialysis. Some nephrology healthcare professionals do not view home dialysis as an option for older adults. Successful delivery of home dialysis for older adults may be made even more difficult by physical or cognitive limitations, concerns around dialysis adequacy, and treatment-related complications, as well as challenges relating to caregiver burnout and patient frailty that are unique to home dialysis and older adults. Ultimately, it would be important for clinicians, patients and their caregivers to define what constitutes a 'successful therapy' to ensure treatment goals are aligned towards each individual's priorities of care, considering the complex challenges that surround an older adult receiving home dialysis. In this review, we evaluate some of the key challenges surrounding the delivery of home dialysis to older adults and propose potential solutions based on updated evidence to overcome these challenges.

Is It Time to Integrate Frailty Assessment in Onconephrology?

Onconephrology has emerged as a novel sub-specialty of nephrology dedicated to the intersection between the kidney and cancer. This intersection is broad and includes a number of important areas of focus, including concurrent chronic kidney disease (CKD) and cancer, acute kidney complications of cancer, and cancer-treatment-induced nephrotoxicity. The importance of onconephrology is even more evident when considering the global growth in the population of older adults, many of whom are living with some degree of frailty. Furthermore, a considerable proportion of older adults have CKD (some of whom eventually progress to kidney failure) and are at high risk of developing solid tumour and hematologic malignancies. Specific to kidney disease, the association between frailty status and kidney disease has been explored in depth, and tools to capture frailty can be used to guide the management and prognostication of older adults living with kidney failure. Whilst there is emerging data regarding the assessment and impact of frailty in onconephrology, there remains a relative paucity of knowledge within this topic. In this article, we evaluate the definition and operationalization of frailty and discuss the significance of frailty within onconephrology. We review evidence on current approaches to assessing frailty in onconephrology and discuss potential developments and future directions regarding the utilization of frailty in this patient population. A greater awareness of the intersections and interactions between frailty and onconephrology and further efforts to integrate frailty assessment in onconephrology to optimize the delivery of realistic and goal-directed management strategies for patients is needed.

Predictors of Urgent Dialysis Following Ambulance Transport to the Emergency Department in Patients Treated With Maintenance Hemodialysis.

Background: Patients receiving maintenance hemodialysis frequently require ambulance transport to the emergency department (ambulance-ED transport). Identifying predictors of outcomes after ambulance-ED transport, especially the need for timely dialysis, is important to health care providers. Objective: The purpose of this study was to derive a risk-prediction model for urgent dialysis after ambulance-ED transport. Design: Observational cohort study. Setting and Patients: All ambulance-ED transports among incident and prevalent patients receiving maintenance hemodialysis affiliated with a regional dialysis program (catchment area of approximately 750 000 individuals) from 2014 to 2018. Measurements: Patients' vital signs (systolic blood pressure, oxygen saturation, respiratory rate, and heart rate) at the time of paramedic transport and time since last dialysis were utilized as predictors for the outcome of interest. The primary outcome was urgent dialysis (defined as dialysis in a monitored setting within 24 hours of ED arrival or dialysis within 24 hours with the first ED patient blood potassium level >6.5 mmol/L) for an unscheduled indication. Secondary outcomes included, hospitalization, hospital length of stay, and in-hospital mortality. Methods: A logistic regression model to predict outcomes of urgent dialysis. Discrimination and calibration were assessed using the C-statistic and Hosmer-Lemeshow test. Results: Among 878 ED visits, 63 (7.2%) required urgent dialysis. Hypoxemia (odds ratio [OR]: 4.04, 95% confidence interval [CI]: 1.75-9.33) and time from last dialysis of 24 to 48 hours (OR: 3.43, 95% CI: 1.05-11.9) and >48 hours (OR: 9.22, 95% CI: 3.37-25.23) were strongly associated with urgent dialysis. A risk-prediction model incorporating patients' vital signs and time from last dialysis had good discrimination (C-statistic 0.8217) and calibration (Hosmer-Lemeshow goodness of fit P value .8899). Urgent dialysis patients were more likely to be hospitalized (63% vs 34%), but there were no differences in inpatient mortality or length of stay. Limitations: Missing data, requires external validation. Conclusion: We derived a risk-prediction model for urgent dialysis that may better guide appropriate transport and care for patients requiring ambulance-ED transport.

Contexte: Les patients sous hémodialyse chronique doivent souvent être transportés au service des urgences par ambulance (transport ambulance-SU). Il est important pour les prestataires de soins de santé que l'on détermine les facteurs prédictifs des résultats après un transport ambulance-SU, en particulier le besoin de dialyze d'urgence. Objectifs: Cette étude visait à établir un modèle de prédiction du risque pour une dialyze d'urgence après un transport ambulance-SU. Type d'étude: Étude de cohorte observationnelle. Participants et cadre de l'étude: Tous les transports ambulance-SU de patients incidents et prévalents recevant une hémodialyse chronique affiliée à un program régional de dialyze (zone desservant environ 750 000 personnes) entre 2014 et 2018. Prédicteurs: Les signes vitaux du patient (pression artérielle systolique, saturation en oxygène, fréquence respiratoire et fréquence cardiaque) au moment du transport par ambulance et le temps écoulé depuis la dernière dialyze. Résultats: La dialyze d'urgence (définie comme une dialyze en environnement monitoré dans les 24 heures suivant l'arrivée aux urgences ou une dialyze dans les 24 heures avec une première mesure du taux de potassium sanguin aux urgences supérieure à 6,5 mmol/L) pour une indication non programmée. Résultats secondaires: hospitalization, durée du séjour à l'hôpital et mortalité à l'hôpital. Méthodologie: Un modèle de régression logistique a servi à prédire le résultat de dialyze d'urgence. La discrimination et la calibration ont été évalués à l'aide de la statistique C et du test Hosmer-Lemeshow. Résultats: Parmi les 878 visites aux urgences, 63 (7,2 %) ont nécessité une dialyze d'urgence. L'hypoxémie (rapport de cote [RC]: 4,04; IC à 95 %: 1,75-9,33) et des périodes de 24 à 48 heures (RC: 3,43; IC à 95 %: 1,05-11,9) et de plus de 48 heures (RC: 9,22; IC à 95 %: 3,37-25,23) depuis la dernière dialyze sont les facteurs qui ont été les plus fortement associés à une dialyze d'urgence. Un modèle de prédiction du risque intégrant les signes vitaux du patient et le temps depuis la dernière dialyze a présenté une bonne discrimination (statistique C: 0,8217) et une bonne calibration (qualité de l'ajustement selon Hosmer-Lemeshow: P =,8899). Les patients qui avaient reçu une dialyze d'urgence étaient plus susceptibles d'être hospitalisés (63% contre 34%), mais aucune différence n'a été observée pour le taux de mortalité ou la durée du séjour en milieu hospitalier. Limites: Données manquantes, validation externe requise. Conclusion: Nous avons dérivé un modèle de prédiction du risque de dialyze d'urgence susceptible de mieux guider le transport et les soins appropriés pour les patients nécessitant un transport ambulance-SU.

Hyperkalemia: Prevalence, Predictors and Emerging Treatments.

It is well established that an elevated potassium level (hyperkalemia) is associated with a risk of adverse events including morbidity, mortality and healthcare system cost. Hyperkalemia is commonly encountered in many chronic conditions including kidney disease, diabetes and heart failure. Furthermore, hyperkalemia may result from the use of renin-angiotensin-aldosterone system inhibitors (RAASi), which are disease-modifying treatments for these conditions. Therefore, balancing the benefits of optimizing treatment with RAASi while mitigating hyperkalemia is crucial to ensure patients are optimally treated. In this review, we will briefly discuss the definition, causes, epidemiology and consequences of hyperkalemia. The majority of the review will be focused on management of hyperkalemia in the acute and chronic setting, emphasizing contemporary approaches and evolving data on the relevance of dietary restriction and the use of novel potassium binders.

The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study.

Background: Post-transplant diabetes mellitus (PTDM) is an important complication after kidney transplantation that results in reduced patient and allograft survival. Although there are established risk factors for PTDM, whether pretransplant C-peptide levels associate with PTDM is unknown. Therefore, in this study, we aimed to examine the association of pretransplant C-peptide levels with PTDM. Methods: This was a cohort study of nondiabetic adult patients who underwent kidney transplant in Nova Scotia, Canada, between January 1, 2016, and March 31, 2021, with fasting C-peptide levels measured before transplant. Multivariable logistic regression was used to determine the association of pretransplant C-peptide (dichotomized around the median) with PTDM at 1 year post transplant. Given the known association between pretransplant obesity and PTDM, we repeated our primary analysis in a cohort restricted to a BMI of 20-35 kg/m2. Results: The median C-peptide value was 3251 (Q1 2480, Q3 4724); pretransplant C-peptide level was dichotomized at 3000 pmol/L. PTDM occurred in 25 (19%) individuals. Thirty percent of patients in the high and only 2% of patients in the low C-peptide groups developed PTDM (P<0.001). A C-peptide level ≥3000 pmol/L was strongly associated with PTDM in multivariable analysis (OR=18.9, 95% CI, 2.06 to 174.2). In a restricted cohort with a BMI of 20-35 kg/m2, an elevated pretransplant C-peptide remained independently associated with the risk of PTDM (OR=15.7, 95% CI, 1.64 to 150.3). C-peptide was the only factor independently associated with PTDM in this restricted BMI cohort. Conclusions: A pretransplant C-peptide level ≥3000 pmol/L was associated with a nearly 20-fold increased odds of PTDM at 1 year post kidney transplantation. Identifying patients with high pretransplant C-peptide levels may therefore help identify those at risk for PTDM who may benefit from focused preventative and therapeutic interventions and support.

Estimated Impact of Deemed Consent Legislation for Organ Donation on Individuals With Kidney Failure: A Dynamic Decision Analytic Model.

Background: There is little data modeling the impact of deemed consent legislation (eligible individuals who do not register their decision to decline to be a donor are presumed to consent after death) on outcomes for individuals with kidney failure. Objective: To estimate the change in life-years (LYs) and quality-adjusted life-years (QALYs) resulting from different changes in the rate of deceased donor kidney transplantation associated with deemed consent legislation and health system transformation. Design: Dynamic Decision Analytic Model. Setting: This modeling study included kidney failure patients in Atlantic Canada (all of whom receive their kidney transplants in Halifax, Nova Scotia). The adoption of deemed consent legislation was the intervention, and opt-in (the status quo) was the reference comparator. Patients: Prevalent kidney failure patients at the end of 2019 in all of Atlantic Canada (N = 3615) served as the starting population. Methods: We compared expected outcomes between the intervention and comparator. Changes in QALYs and total LYs were modeled under different changes to the proportion of patients receiving a deceased donor kidney transplant (from -10% to 20%) resulting from deemed consent relative to the status quo. Changes in QALYs and LYs were reported for 3 different time horizons (5, 10, and 30 years). Uncertainty around QALYs and total LYs was reported using 95% confidence intervals (CIs) constructed from a probabilistic sensitivity analysis using 1000 Monte Carlo Simulations. Results: The increase in QALYs ranged from 7 QALYs (95% CI: 5-10) with a 5% increase using a 5-year time frame to 882 QALYs (95% CI: 619-1144) with a 20% increase over a 30-year time frame. Parallel changes in total LYs were also observed. In contrast, decreases in deceased donor kidney transplantation resulted in a loss of QALYs (for example, -463 QALYs; 95% CI: -633 to -306 for a 10% decrease over a 30-year time frame). Using the most optimistic scenario (a 20% increase), there was an 18% increase in the cumulative number of deceased donor kidney transplant recipients over a 30-year observation period. Limitations: The results are subject to uncertainty depending on changes to the dialysis or transplant population that were not modeled and that may not be fully captured with probabilistic sensitivity analysis. Conclusions: Deemed consent legislation will lead to variable changes in QALYs and total LYs for the kidney failure population, depending on the degree to which deceased donor transplantation rates change and the time horizon of observation. This modeling study may serve as a baseline to monitor the future impact of deemed consent legislation.

Contexte: Il existe peu de données modélisant l'impact d'une loi sur le consentement présumé (les personnes admissibles qui n'enregistrent pas leur décision de refuser d'être un donneur sont présumées consentir après leur décès) sur les résultats des personnes atteintes d'insuffisance rénale. Objectif: Estimer les variations dans les années de vie (AV) et les années de vie corrigées en fonction de leur qualité (AVCQ) résultant de changements dans les taux de transplantation rénale provenant d'un donneur décédé; changements qui seraient associés à la loi sur le consentement présumé et à la transformation du système de santé. Conception: Modèle dynamique d'analyse décisionnelle. Cadre: L'étude a été modélisée avec des patients du Canada atlantique atteints d'insuffisance rénale terminale (tous avaient reçu leur greffe de rein à Halifax, en Nouvelle-Écosse). L'intervention consistait en l'adoption d'une loi sur le consentement présumé, alors que le statu quo représentait le comparateur de référence. Sujets: La population de départ était constituée des patients atteints d'insuffisance rénale terminale à la fin de 2019 dans l'ensemble du Canada atlantique (N=3615). Méthodologie: Nous avons comparé les résultats attendus pour l'intervention et le comparateur. Les variations dans les AVCQ et les AV totales ont été modélisées en fonction de divers changements résultant du consentement présumé par rapport au statu quo dans la proportion de patients recevant une transplantation rénale d'un donneur décédé (de -10 à 20 %). Les variations dans les AVCQ et les AV ont été rapportées pour trois horizons temporels (5, 10 et 30 ans). L'incertitude entourant les AVCQ et les années de vie totales a été rapportée avec des intervalles de confiance à 95 % établis à partir d'une analyse de sensibilité probabiliste réalisée par la méthode de Monte Carlo. Résultats: En ce qui concerne les AVCQ, la variation passait de 7 AVCQ (IC 95 % : 5, 10), avec une augmentation de 5 % sur une période de 5 ans, à 882 AVCQ (IC 95 % : 619, 1 144) avec une augmentation de 20 % sur une période de 30 ans. Des variations parallèles ont été observées pour les AV totales. En revanche, la diminution du taux de transplantations rénales provenant d'un donneur décédé a entraîné une perte d'AVCQ (par ex. - 463 AVQ; IC à 95 % : -633, -306 pour une diminution de 10 % sur une période de 30 ans). Dans le scénario le plus optimiste (augmentation de 20 %), on a observé une augmentation de 18 % du nombre cumulatif de transplantations rénales provenant de donneurs décédés au cours d'une période d'observation de 30 ans. Limites: Les résultats sont sujets à des incertitudes en fonction de variations dans la population de patients sous dialyse ou greffés qui n'auraient pas été modélisées et qui pourraient ne pas être entièrement prises en compte par une analyse de sensibilité probabiliste. Conclusion: La loi sur le consentement présumé entraînera des changements variables dans les AV totales et les AVCQ des patients atteints d'insuffisance rénale terminale, selon le degré d'évolution des taux de transplantation provenant de donneurs décédés et de l'horizon d'observation. Cette étude de modélisation peut servir de référence pour surveiller les impacts futurs d'une loi sur le consentement présumé.

Combined Donor-Recipient Obesity and the Risk of Graft Loss After Kidney Transplantation.

Background: As the prevalence of obesity increases globally, appreciating the effect of donor and recipient (DR) obesity on graft outcomes is of increasing importance. Methods: In a cohort of adult, kidney transplant recipients (2000-2017) identified using the SRTR, we used Cox proportional hazards models to examine the association between DR obesity pairing (body mass index (BMI) >30 kg/m2), and death-censored graft loss (DCGL) or all-cause graft loss, and logistic regression to examine risk of delayed graft function (DGF) and ≤30 days graft loss. We also explored the association of DR weight mismatch (>30 kg, 10-30 kg (D>R; D

Comparing the Net Benefits of Adult Deceased Donor Kidney Transplantation for a Patient on the Preemptive Waiting List vs a Patient Receiving Dialysis.

Importance: Preemptive kidney transplantation is the preferred treatment for end-stage kidney disease. However, deceased donor (DD) kidneys are limited, and the net benefit of allocating kidneys to a preemptively waitlisted patient rather than to a patient receiving dialysis is unclear. Objective: To estimate the net benefit and costs of allocating kidneys to preemptively waitlisted patients vs those receiving dialysis. Design, Setting, and Participants: This medical decision analytical model used data from the 2020 US Renal Data System to calculate patient survival among waitlisted patients who received a DD kidney transplant. Four patients were simulated, with similar characteristics: (1) a patient on the preemptive waiting list receiving a DD transplant, (2) a patient on the preemptive waiting list never receiving a transplant, (3) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) receiving a transplant, and (4) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) never receiving a transplant. Annual probability of initiating dialysis (for patients 1 and 2) and duration of dialysis (for patients 3 and 4) were varied in sensitivity analyses. Exposures: Allocating a DD kidney to a patient on the preemptive waiting list vs the same kidney to a patient receiving dialysis for less than 1 year, with similar recipient characteristics. Main Outcomes and Measures: Differences in projected quality-adjusted life-years (QALYs) and total costs. Results: In a simulated patient with a mean start age of 50 years (range, 30-64 years), the patient receiving a preemptive DD transplantation experienced 10.58 (95% CI, 10.36-10.80) QALYs, and the patient on the preemptive waiting list never transplanted experienced 6.83 (95% CI, 6.67-6.99) QALYs. The patient receiving DD transplantation after less than 1 year of dialysis experienced 10.33 (95% CI, 10.21-10.55) QALYs, and the patient receiving dialysis who remained on the waiting list experienced 6.20 (95% CI, 6.04-6.36) QALYs; allocating a DD kidney to the preemptive patient added 3.75 (95% CI, 3.57-3.93) QALYs, whereas allocating the kidney to the patient already receiving dialysis added 4.13 (95% CI, 3.92-4.31) QALYs. While the estimated posttransplant survival was longest for the preemptive transplant recipient, preferentially allocating the kidney to the preemptive patient results in 0.39 (95% CI, 0.49-0.29) fewer QALYs. The net cost of preemptive transplantation was $54 100 (95% CI, $44 100-$64 100) more than transplantation to a waitlisted patient. If the rate of transitioning to dialysis was 20 (rather than 33) events per 100 patient waiting list-years, the net QALYs were -0.67 (95% CI, -0.78 to -0.56). If the patient was receiving dialysis for 3 to 4 years (vs <1 year) the net benefit was not significantly different; however, net costs were considerably higher for the preemptive option. Conclusions and Relevance: In this decision analytic model study, although allocating DD kidneys to patients preemptively was the best option from a patient perspective, allocating DD kidneys to patients receiving dialysis was a better use of a scare resource from a societal perspective.

Predictors of Hyperkalemia among Patients on Maintenance Hemodialysis Transported to the Emergency Department by Ambulance.

Background: Hyperkalemia is common among patients on maintenance hemodialysis (HD) and is associated with mortality. We hypothesized that clinical characteristics available at time of paramedic assessment before emergency department (ED) ambulance transport (ambulance-ED) would associate with severe hyperkalemia (K≥6 mmol/L). Rapid identification of patients who are at risk for hyperkalemia and thereby hyperkalemia-associated complications may allow paramedics to intervene in a timely fashion, including directing emergency transport to dialysis-capable facilities. Methods: Patients on maintenance HD from a single paramedic provider region, who had at least one ambulance-ED and subsequent ED potassium from 2014 to 2018, were examined using multivariable logistic regression to create risk prediction models inclusive of prehospital vital signs, days from last dialysis, and the presence of prehospital electrocardiogram (ECG) features of hyperkalemia. We used bootstrapping with replacement to validate each model internally, and performance was assessed by discrimination and calibration. Results: Among 704 ambulance-ED visits, severe hyperkalemia occurred in 75 (11%); 26 patients with ED hyperkalemia did not have a prehospital ECG. Younger age at transport, longer HD vintage, more days from last hemodialysis session (OR=49.84; 95% CI, 7.72 to 321.77 for ≥3 days versus HD the same day [before] ED transport), and prehospital ECG changes (OR=6.64; 95% CI, 2.31 to 19.12) were independently associated with severe ED hyperkalemia. A model incorporating these factors had good discrimination (c-statistic 0.82; 95% CI, 0.76 to 0.89) and, using a cutoff of 25% probability, correctly classified patients 89% of the time. Conclusions: Characteristics available at the time of ambulance-ED were associated with severe ED hyperkalemia. An awareness of these associations may allow health care providers to define novel care pathways to ensure timely diagnosis and management of hyperkalemia.

Can Peer Review Be Kinder? Supportive Peer Review: A Re-Commitment to Kindness and a Call to Action.

Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology "supportive review."

L'évaluation par les pairs vise à sélectionner les articles à publier et à en améliorer le contenu avant publication. Nous sommes d'avis que ce processus peut être fait avec bienveillance sans perdre en rigueur. En 2014, l'équipe de rédaction fondatrice du Canadian Journal of Kidney Health and Disease (CJKHD) a pris l'engagement ferme de traiter les auteurs comme ses membres souhaiteraient eux-mêmes être traités. Aujourd'hui, notre groupe élargi d'auteur(e)s réaffirme ce principe pour lequel nous proposons la terminologie « évaluation constructive ¼.

The Canadian Glomerulonephritis Registry (CGNR) and Translational Research Initiative: Rationale and Clinical Research Protocol.

Background: Glomerulonephritis (GN) is a leading cause of kidney failure and accounts for 20% of incident cases of end-stage kidney disease (ESKD) in Canada annually. Reversal of kidney injury and prevention of progression to kidney failure is possible; however, limited knowledge of underlying disease mechanisms and lack of noninvasive biomarkers and therapeutic targets are major barriers to successful therapeutic intervention. Multicenter approaches that link longitudinal clinical and outcomes data with serial biologic specimen collection would help bridge this gap. Objective: To establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in GN in Canada. Design: Multicenter, prospective observational registry, starting in 2019. Setting: Nine participating Canadian tertiary care centers. Patients: Adult patients with a histopathologic pattern of injury consistent with IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy, C3 glomerulopathy, and membranoproliferative GN recruited within 24 months of biopsy. Measurements: Initial visits include detailed clinical, histopathological, and laboratory data collection, blood, urine, and tonsil swab biospecimen collection, and a self-administered quality of life questionnaire. Follow-up clinical and laboratory data collection, biospecimen collection, and questionnaires are obtained every 6 months thereafter. Methods: Patients receive care as defined by their physician, with study visits scheduled every 6 months. Patients are followed until death, dialysis, transplantation, or withdrawal from the study. Key outcomes include a composite of ESKD or a 40% decline in estimated glomerular filtration rate (eGFR) at 2 years, rate of kidney function decline, and remission of proteinuria. Clinical and molecular phenotypical data will be analyzed by GN subtype to identify disease predictors and discover therapeutic targets. Limitations: Given the relative rarity of individual glomerular diseases, one of the major challenges is patient recruitment. Initial registry studies may be underpowered to detect small differences in clinically meaningful outcomes such as ESKD or death due to small sample sizes and short duration of follow-up in the initial 2-year phase of the study. Conclusions: The Canadian Glomerulonephritis Registry (CGNR) supports national collaborative efforts to study glomerular disease patients and their outcomes. Trial registration: NCT03460054.

Contexte: Les glomérulonéphrites (GN) sont des causes importantes d'insuffisance rénale; elles représentent 20 % des cas incidents d'insuffisance rénale terminale (IRT) au Canada chaque année. Inverser la néphropathie et prévenir la progression vers l'insuffisance rénale est possible, mais deux obstacles majeurs freinent la réussite de l'intervention thérapeutique: une compréhension limitée des mécanismes sous-jacents de la maladie, de même que l'absence de biomarqueurs non invasifs et de cibles thérapeutiques. Les approches multicentriques reliant les données cliniques longitudinales et les résultats de santé à la collecte d'échantillons biologiques en série permettraient de combler cette lacune. Objectif: Créer une base de données cliniques nationale en ligne, multidimensionnelle et axée sur le patient, de même qu'une biobanque virtuelle fédérée pour permettre de mener des recherches moléculaires et cliniques humaines sur les GN au Canada. Type d'étude: Registre d'observation prospectif multicentrique débuté en 2019. Cadre: Neuf centres de soins tertiaires canadiens. Sujets: Des patients adultes recrutés dans les 24 mois suivant la biopsie et présentant un profil histopathologique de lésion compatible avec une néphropathie à IgA, une hyalinose segmentaire et focale, une maladie à changement minime, une glomérulonéphrite extra-membraneuse, une glomérulopathie à C3 et une glomérulonéphrite membranoproliférative. Mesures: La première visite comporte une collecte détaillée des données cliniques, histopathologiques et de laboratoire, la collecte d'échantillons biologiques (sang, urine et écouvillonnage des amygdales), ainsi qu'un questionnaire autoadministré sur la qualité de vie. Pour le suivi, la collecte des données cliniques et de laboratoire, la collecte des échantillons biologiques et les questionnaires s'effectuent tous les six mois. Méthodologie: Les patients reçoivent des soins comme établi par leur médecin, et les visites d'étude sont programmées tous les six mois. Les patients sont suivis jusqu'au décès ou jusqu'à la dialyse, à la transplantation ou au retrait de l'étude. Un critère de jugement combiné (IRT, ou diminution de 40 % du débit de filtration glomérulaire estimé après deux ans), ainsi que le taux de déclin de la fonction rénale et la rémission de la protéinurie sont les principaux critères de jugement. Les données phénotypiques cliniques et moléculaires seront analysées par sous-types de GN afin d'identifier les prédicteurs de la maladie et de découvrir de nouvelles cibles thérapeutiques. Limites: Le recrutement des sujets demeure un des principaux défis puisque les maladies glomérulaires prises individuellement sont relativement rares. La faible taille des échantillons et la courte durée du suivi pendant les deux ans de la phase initiale de l'étude pourraient faire en sorte que les études initiales issues du registre ne soient pas assez puissantes pour détecter de légères différences dans les résultats cliniquement significatifs comme l'IRT ou le décès. Conclusion: Le Canadian Glomerulonephritis Registry (CGNR) appuie les efforts de collaboration nationale visant à étudier les patients atteints de maladies glomérulaires et leur évolution clinique. Enregistrement de l'essai: NCT03460054.

Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort Study.

Background: The dialysis treatment day after the 2-day interdialytic interval (Monday/Tuesday) is associated with a heightened risk of hospitalization for patients on in-center hemodialysis (ICHD). In this national cohort study, we sought to characterize hospitalizations by day of the week for patients receiving ICHD, home HD (HHD), and peritoneal dialysis (PD) and to identify whether there were differences in the probability of a Monday/Tuesday admission for each modality type. Methods: Patients on maintenance dialysis in Canada were analyzed from 2005 to 2014 using the Canadian Organ Replacement Register. Patients on hemodialysis were categorized as those receiving ICHD, HHD, frequent ICHD, or frequent HHD (the latter two included short daily and nocturnal HD). Hospitalizations were attributed to the previous treatment if they occurred within 30 days of a treatment change. Differences in the proportion of patients experiencing a Monday/Tuesday admission with all other days of the week were compared using a generalized linear model with binomial distribution and reported using adjusted odds ratios (OR) with 95% CIs. Results: Overall, 27,430 individuals experienced 111,748 hospitalization episodes. Rates per 1000 patient days were 3.76, 2.98, 2.71, 2.16, and 2.13 for each of frequent ICHD, ICHD, PD, HHD, and frequent HHD, respectively. Compared with those on ICHD, only patients receiving frequent HHD (OR, 0.89; 95% CI, 0.81 to 0.97) and PD (OR, 0.95; 95% CI, 0.93 to 0.97) had a lower odds of experiencing a Monday/Tuesday admission. The OR was lower when restricted to hospitalization episodes for cardiovascular reasons comparing frequent HHD with ICHD (OR, 0.68; 95% CI, 0.48 to 0.96). Conclusion: In this nationally representative cohort, we identified that the probability of a Monday/Tuesday admission was lower for frequent HHD and PD compared with ICHD, most notably for hospitalizations due to cardiovascular causes. Gaining a better understanding of the reasons behind this observation may help to develop future strategies to reduce overall and cause-specific hospitalization for patients receiving dialysis.

Disparities in Access to Preemptive Repeat Kidney Transplant: Still Missing the Mark?

Background: The need for repeat transplant due to failing kidney allografts is increasing over time. The benefit of preemptive kidney retransplant (PKre-T) is controversial. Marginalized populations are less likely to undergo their first transplant preemptively; however, whether inequities exist for those undergoing PKre-T is unknown. Methods: We performed a cohort study of adult patients undergoing live and deceased kidney transplant in the United States from 2000 to 2018 identified using the Scientific Registry of Transplant Recipients, and we identified patients with first preemptive kidney transplant (PKT) and PKre-T. In the primary analysis, a multivariable logistic regression was used to identify independent predictors of PKre-T. In secondary analyses, multivariable Cox models were used to determine the association of PKre-T with death-censored and all-cause graft loss. Results: In total, 4910 (15.5%) patients underwent PKre-T, and 43,293 (19.1%) underwent first PKT. Inequities in access to PKre-T persisted (OR, 0.49; 95% CI, 0.44 to 0.55 for unemployed versus full time; OR, 1.61; 95% CI, 1.14 to 2.25 for graduate school versus not completing high school; OR, 0.61; 95% CI, 0.52 to 0.70 for Black versus White race); 7.1% of all transplanted Black patients received PKre-T versus 17.4% of White patients. Women were more likely to undergo PKre-T than men (OR, 1.42; 95% CI, 1.29 to 1.57). PKre-T was associated with superior graft survival relative to retransplant after a period of dialysis (HR, 0.73; 95% CI, 0.67 to 0.80 for all-cause graft failure; HR, 0.72; 95% CI, 0.65 to 0.81 for death-censored graft loss). Conclusions: Despite improved patient and graft survival, inequities in access to PKre-T persist. Patients with lower education, patients with reduced employment status, patients of Black race, and men are less likely to receive PKre-T.