Systematic Review of Women Leading and Participating in Nephrology Randomized Clinical Trials.

Introduction: Women are underrepresented in the leadership of and participation in randomized controlled trials (RCTs). We conducted a bibliometric review of nephrology RCTs to examine trial leadership by women and participation of women in nephrology RCTs. Methods: A bibliometric review of RCTs published in top medical, surgical, or nephrology journals was conducted using MEDLINE and EMBASE from January 2011 to December 2021. Leadership by women as corresponding authors, women trial participation, and trial characteristics were examined with duplicate independent data extraction. Logistic regression was used to examine associations between trial characteristics and women leadership and trial participation. Results: A total of 1770 studies were screened and 395 RCTs met eligibility criteria. The number (%) of women in corresponding, first, and last authorship positions were as follows: 89 (22%), 109 (28%), and 74 (19%), respectively, without change over time (P = 0.94). The median percentage (interquartile range [IQR]) of women trial participants was 39.0% (13.5%) with no difference between women or men lead authors (P = 0.15). Men lead authors were statistically less likely to enroll women in RCTs. Women lead authors were less likely to be funded by industry (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14-0.63; P = 0.002) or lead international trials (OR: 0.11; 95% CI: 0.01-0.83; P = 0.03). Trials with sex-specific eligibility criteria were more likely to have women leaders (OR: 2.56; 95% CI: 1.19-5.49; P = 0.02) than those without. Discussion: Gender inequalities in RCT leadership and RCT participation exist in nephrology and did not improve over time. Strategies to improve inequalities need to be implemented and evaluated.

Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

Implementation of a 1-Day Living Kidney Donor Evaluation Program: A Qualitative Analysis of Donor Candidate and Stakeholder Perspectives.

Introduction: A lengthy donor evaluation process hinders living donor kidney transplantation (LDKT). At The Ottawa Hospital, 1-day evaluation process was recently developed, with a goal to accelerate the determination of donor suitability. The major objective of this study was to solicit feedback from donor candidates and key stakeholders who participated in the 1-day living kidney donor evaluation process, to determine the program's acceptability and factors influencing its implementation elsewhere. Methods: Semi-structured interviews were conducted with donor candidates who participated in the 1-day living kidney donor evaluation process, and with stakeholders who are instrumental to the implementation strategy. Interviews were conducted via videoconference or by telephone from May 2022 to December 2022. Directed content analysis was conducted using 2 unique frameworks for stakeholder and donor candidate interviews. Results: Our study included 13 stakeholders and 18 donor candidates, of whom 16 (89%) were women and 7 (39%) proceeded to kidney donation. Eighteen (100%) perceived the process to be both time-effective and cost-effective, due to reduced travel and missed work time. Thirteen (72%) felt that the 1-day evaluation may accelerate determination of donor suitability. Sequential virtual sessions with a nurse and social worker in advance of the evaluation day were seen as providing critical education and support. Among stakeholders, 11 (85%) emphasized donor candidate care and faster candidacy determinations. Conclusion: The 1-day evaluation process was preferred by most donor candidates, and was perceived as time-effective and cost-effective by most interviewees. An expedited, 1-day evaluation may accelerate determination of donor suitability and improve LDKT rates.

Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and meta-analysis.

INTRODUCTION: Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion. OBJECTIVES: To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings. METHODS: We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible. RESULTS: The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported. DISCUSSION: Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol. CONCLUSIONS: The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes. REGISTRATION: This systematic review protocol is registered at PROSPERO, CRD42018101955.

Kidney function, cardiovascular outcomes and survival of living kidney donors with hypertension: a systematic review protocol.

INTRODUCTION: Hypertension has been considered a contraindication for living kidney donation in the past. Since transplantation from living kidney donors remains the best modality for kidney failure, there is now an increased acceptance of living kidney donors with hypertension. However, the safety of this practice for the cardiovascular and kidney health of the donor is unclear. We will conduct a systematic review to summarise and synthesise the existing literature on this topic. METHODS AND ANALYSIS: A systematic review of prospective randomised and non-randomised and retrospective studies will be conducted. MEDLINE, EMBASE, Cochrane CENTRAL and EBM reviews published from January 1946 to December 2021 will be reviewed. Primary outcome will be the difference in the survival, major adverse cardiovascular events, estimated glomerular filtration rate of 45 mL/min or less and development of end-stage kidney failure, between living kidney donors with and without hypertension. Study screening, selection, and data extraction will be performed by two independent reviewers. Studies must fulfil all eligibility criteria for inclusion into the systematic review and meta-analysis. The Risk of Bias in Non-Randomised studies tool will be used to assess bias. ETHICS AND DISSEMINATION: No ethical approval is required for this systematic review. The results of this review will be disseminated in a peer-reviewed, open-access journal to ensure access to all stakeholders in kidney transplantation and to inform clinical guidelines on the evaluation and follow-up care of living kidney donor candidates. PROSPERO REGISTRATION NUMBER: CRD42022300119.

Analysis of Electrolyte Abnormalities in Adolescents and Adults and Subsequent Diagnosis of an Eating Disorder.

Importance: Eating disorders lead to increased mortality and reduced quality of life. While the acute presentations of eating disorders frequently involve electrolyte abnormalities, it remains unknown whether electrolyte abnormalities may precede the future diagnosis of an eating disorder. Objective: To determine whether outpatient electrolyte abnormalities are associated with the future diagnosis of an eating disorder. Design, Setting, and Participants: This population-level case-control study used provincial administrative health data for residents of Ontario, Canada aged 13 years or older from 2008 to 2020. Individuals without an eating disorder (controls) were matched 4:1 to individuals diagnosed with an incident eating disorder (cases) based on age and sex. Both groups had outpatient electrolyte measurements between 3 years and 30 days prior to index. Index was defined as the date of an eating disorder diagnosis in any inpatient or outpatient clinical setting for cases. Controls were assigned a pseudo-index date according to the distribution of index dates in the case population. Individuals with any prior eating disorder diagnosis were excluded. The data analyzed was from January 1, 2008, through June 30, 2020. Exposures: Any electrolyte abnormality, defined as abnormal test results for a composite of hypokalemia, hyperkalemia, hyponatremia, hypernatremia, hypomagnesemia, hypophosphatemia, metabolic acidosis, or metabolic alkalosis. Outcomes and Measures: Eating disorder diagnosis including anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified. Results: A total 6970 eligible Ontario residents with an eating disorder (mean [SD] age, 28 (19) years; 6075 [87.2%] female, 895 [12.8%] male) were matched with 27 878 age- and sex-matched residents without an eating disorder diagnosis (mean [SD] age, 28 [19] years; 24 300 [87.2%] female, 3578 [12.8%] male). Overall, 18.4% of individuals with an eating disorder had a preceding electrolyte abnormality vs 7.5% of individuals without an eating disorder (adjusted odds ratio [aOR], 2.12; [95% CI, 1.86-2.41]). The median (IQR) time from the earliest electrolyte abnormality to eating disorder diagnosis was 386 (157-716) days. Specific electrolyte abnormalities associated with a higher risk of an eating disorder were: hypokalemia (aOR, 1.98; 95% CI, 1.70-2.32), hyperkalemia (aOR, 1.97; 95% CI, 1.48-2.62), hyponatremia (aOR, 5.26; 95% CI, 3.32-8.31), hypernatremia (aOR, 3.09; 95% CI, 1.01-9.51), hypophosphatemia (aOR, 2.83; 95% CI, 1.82-4.40), and metabolic alkalosis (aOR, 2.60; 95% CI, 1.63-4.15). Conclusions and Relevance: In this case-control study, individuals with an eating disorder were associated with a preceding outpatient electrolyte abnormality compared with matched controls. Otherwise unexplained electrolyte abnormalities may serve to identify individuals who may benefit from screening for an underlying eating disorder.

Comparison of Clinical Outcomes and Safety Associated With Chlorthalidone vs Hydrochlorothiazide in Older Adults With Varying Levels of Kidney Function.

Importance: Thiazide diuretics are commonly prescribed for the treatment of hypertension, a disease highly prevalent among older individuals and in those with chronic kidney disease. How specific thiazide diuretics compare in regard to safety and clinical outcomes in these populations remains unknown. Objective: To compare safety and clinical outcomes associated with chlorthalidone or hydrochlorothiazide use among older adults with varying levels of kidney function. Design, Setting, and Participants: This population-based retrospective cohort study was conducted in Ontario, Canada, from 2007 to 2015. Participants included adults aged 66 years or older who initiated chlorthalidone or hydrochlorothiazide during this period. Data were analyzed from December 2019 through September 2020. Exposures: New chlorthalidone users were matched 1:4 with new hydrochlorothiazide users by a high-dimensional propensity score. Time-to-event models accounting for competing risks examined the associations between chlorthalidone vs hydrochlorothiazide use and the outcomes of interest overall and within estimated glomerular filtration rate (eGFR) categories (≥60, 45-59, and <45 mL/min/1.73 m2). Main Outcomes and Measures: The outcomes of interest were adverse kidney events (ie, eGFR decline ≥30%, dialysis, or kidney transplantation), cardiovascular events (composite of myocardial infarction, coronary revascularization, heart failure, or atrial fibrillation), all-cause mortality, and electrolyte anomalies (ie, sodium or potassium levels outside reference ranges). Results: After propensity score matching, the study cohort included 12 722 adults (mean [SD] age, 74 [7] years; 7063 [56%] women; 5659 [44%] men; mean [SD] eGFR, 69 [19] mL/min/1.73 m2), including 2936 who received chlorthalidone and 9786 who received hydrochlorothiazide. Chlorthalidone use was associated with a higher risk of eGFR decline of 30% or greater (hazard ratio [HR], 1.24 [95% CI, 1.13-1.36]) and cardiovascular events (HR, 1.12 [95% CI, 1.04-1.22]) across all eGFR categories compared with hydrochlorothiazide use. Chlorthalidone use was also associated with a higher risk of hypokalemia compared with hydrochlorothiazide use, which was more pronounced among those with higher eGFR (eGFR ≥60 mL/min/1.73 m2: HR, 1.86 [95% CI, 1.67-2.08]; eGFR 45-59 mL/min/1.73 m2: HR, 1.57 [95% CI, 1.25-1.96]; eGFR <45 mL/min/1.73 m2: HR, 1.10 [95% CI, 0.84-1.45]; P for interaction = .001). No significant differences were observed between chlorthalidone and hydrochlorothiazide for dialysis or kidney transplantation (HR, 1.44 [95% CI, 0.88-2.36]), all-cause mortality (HR, 1.10 [95% CI, 0.93-1.29]), hyperkalemia (HR, 1.05 [95% CI, 0.79-1.39]), or hyponatremia (HR, 1.14 [95% CI, CI 0.98-1.32]). Conclusions and Relevance: This cohort study found that among older adults, chlorthalidone use was associated with a higher risk of eGFR decline, cardiovascular events, and hypokalemia compared with hydrochlorothiazide use. The excess risk of hypokalemia with chlorthalidone was attenuated in participants with reduced kidney function. Placed in context with prior observational studies comparing the safety and clinical outcomes associated with thiazide diuretics, these results suggest that there is no evidence to prefer chlorthalidone over hydrochlorothiazide.

The impact of measuring split kidney function on post-donation kidney function: A retrospective cohort study.

BACKGROUND: Studies have reported agreement between computed tomography (CT) and renography for the determination of split kidney function. However, their correlation with post-donation kidney function remains unclear. We compared CT measurements with renography in assessment of split kidney function (SKF) and their correlations with post-donation kidney function. METHODS: A single-centre, retrospective cohort study of 248 donors from January 1, 2009-July 31, 2019 were assessed. Pearson correlations were used to assess post-donation kidney function with renography and CT-based measurements. Furthermore, we examined high risk groups with SKF difference greater than 10% on renography and donors with post-donation eGFR less than 60 mL/min/1.73m2. RESULTS: 62% of donors were women with a mean (standard deviation) pre-donation eGFR 99 (20) and post-donation eGFR 67 (22) mL/min/1.73m2 at 31 months of follow-up. Post-donation kidney function was poorly correlated with both CT-based measurements and renography, including the subgroup of donors with post-donation eGFR less than 60 mL/min/1.73m2 (r less than 0.4 for all). There was agreement between CT-based measurements and renography for SKF determination (Bland-Altman agreement [bias, 95% limits of agreement] for renography vs: CT volume, 0.76%, -7.60-9.15%; modified ellipsoid,1.01%, -8.38-10.42%; CC dimension, 0.44%, -7.06-7.94); however, CT missed SKF greater than 10% found by renography in 20 out 26 (77%) of donors. CONCLUSIONS: In a single centre study of 248 living donors, we found no correlation between CT or renography and post-donation eGFR. Further research is needed to determine optimal ways to predict remaining kidney function after donation.

Initial and Recurrent Hyperkalemia Events in Patients With CKD in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The risk of hyperkalemia is elevated in chronic kidney disease (CKD); however, the initial and recurrent risk among older individuals is less clear. OBJECTIVES: We set out to examine the initial and 1-year recurrent risk of hyperkalemia by level of kidney function (estimated glomerular filtration rate, eGFR) in older adults (≥66 years old). DESIGN: Population-based, retrospective cohort study. SETTINGS: Ontario, Canada. PARTICIPANTS: 905 167 individuals (≥66 years old) from 2008 to 2015. MEASUREMENTS: Serum potassium values. METHODS: Individuals were stratified by eGFR (≥90, 60-89, 30-59, 15-29 mL/min/1.73 m2) and examined for the risk of incident hyperkalemia (K ≥ 5.5 mEq/L) using adjusted Cox proportional hazards models. The 1-year risk of recurrent hyperkalemia was examined using multivariable Andersen-Gill models. RESULTS: Among a population of 905 167 individuals (15% eGFR ≥ 90, 58% eGFR 60-89, 25% eGFR 30-59, 3% eGFR 15-29) with a potassium measurement, there were a total of 18 979 (2.1%) individuals with hyperkalemia identified. The event rate (per 1000 person-years) and adjusted hazard ratio (HR) of hyperkalemia was inversely associated with eGFR (mL/min; eGFR >90 mL/min: 8.8, referent, 60-89 mL/min: 11.8 HR 1.41; eGFR 30-59: 39.8, HR 4.37; eGFR 15-29: 133.6, 13.65) and with an increasing urine albumin-to-creatinine ratio (ACR, mg/mmol; ACR< 3: 14, referent, ACR 3-30: 35.1, HR 1.98; ACR >30: 93.7, 4.71). The 1-year event rate and adjusted risk of recurrent hyperkalemia was similarly inversely associated with eGFR (eGFR ≥ 90: 10.1, referent, eGFR 60-89: 14.4, HR 1.47; eGFR 30-59: 54.8, HR 4.90; eGFR 15-29: 208.0, HR 12.98). Among individuals with a baseline eGFR of 30 to 59 and 15 to 29, 0.9 and 3.8% had greater than 2 hyperkalemia events. The relative risk of initial and recurrent hyperkalemia was marginally higher with RAAS blockade. Roughly 1 in 4 individuals with hyperkalemia required hospitalization the day of or within 30 days after their hyperkalemia event. LIMITATIONS: Limited to individuals aged 66 years and above. CONCLUSIONS: Patients with low eGFR are at a high risk of initial and recurrent hyperkalemia. TRIAL REGISTRATION: N/A.

CONTEXTE: Le risque d'hyperkaliémie est élevé en contexte d'insuffisance rénale chronique (IRC). On en sait cependant peu sur le risque initial et récurrent d'hyperkaliémie chez les patients âgés. OBJECTIF: Nous avons examiné le risque initial d'hyperkaliémie et le risque de récurrence sur une année selon le niveau de fonction rénale (débit de filtration glomérulaire estimé [DFGe]) chez les patients âgés (plus de 66 ans). TYPE D'ÉTUDE: Étude de cohorte rétrospective basée sur une population. CADRE: Ontario, Canada. SUJETS: L'étude porte sur un total de 905 167 individus (âgés de 66 ans et plus) entre 2008 et 2015. MESURES: Les valeurs de potassium sérique. MÉTHODOLOGIE: Les individus ont été stratifiés en fonction du DFGe (≥90, 60-89, 30-59, 15-29 ml/min/1.73m2) et examinés pour le risque d'hyperkaliémie incidente (K ≥ 5,5 mEq/L) à l'aide de modèles de risques proportionnels de Cox corrigés. Le risque de récurrence sur un an a été examiné avec des modèles multivariés d'Andersen-Gill. RÉSULTATS: Parmi les 905 167 individus disposant d'une mesure de potassium sérique (15 % avec un DFGe ≥ 90; 58 % avec un DFGe de 60-89; 25 % avec un DFGe de 30-59; et 3 % avec un DFGe de 15-29), on a recensé 18 979 individus (2,1 %) présentant une hyperkaliémie. Le taux d'événements (pour 1 000 années-personnes) et le rapport de risque corrigé (RR) de l'hyperkaliémie étaient inversement associés au DFGe (ml/min). Ainsi, un DFGe > 90 ml/min a été associé à 8,8 événements pour 1 000 années-personnes (EV) et constituait le référent pour le RR; ces valeurs pour les autres niveaux de DFGe étaient les suivantes: 11,8 EV (RR = 1,41) pour un DFGe 60-89; 39,8 EV (RR = 4,37) pour un DFGe de 30-59; et 133,6 EV (RR = 13,65) pour un DFGe de 15-29. L'accroissement de ces valeurs a également été associé à un accroissement du rapport albumine/créatinine dans l'urine (RAC mg/mmol). Ainsi, un RAC < 3 a été associé à 14 EV et constituait le référent pour le RR, tandis que 35,1 EV (RR = 1,98) ont été observés pour un RAC de 3-30; et que ce nombre passait à 93,7 EV (RR=4,71) pour un RAC > 30. Le taux d'événements sur un an et le risque corrigé d'hyperkaliémie récidivante étaient eux aussi inversement associés au DFGe: 10,1 EV (RR = valeur de référence) pour un DFGe ≥ 90; 14,4 EV (RR=1,47) pour un DFGe 60-89; 54,8 EV (RR=4,90) pour un DFGe 30-59; et 208,0 EV (RR=12,98) pour un DFGe 15-29. Parmi les individus présentant un DFGe initial de 30-59 et de 15-29 ml/min/1,73m2, un certain nombre de patients avaient vécu plus de deux événements d'hyperkaliémie (respectivement 0,9 % et 3,8 %). Le risque relatif d'hyperkaliémie initiale et récurrente était légèrement plus élevé avec le blocage du SRAA. Environ une personne sur quatre atteinte d'hyperkaliémie a dû être hospitalisée le jour de l'événement ou dans les 30 jours suivant celui-ci. LIMITES: L'étude a été limitée aux personnes âgées de 66 ans et plus. CONCLUSION: Les patients présentant un faible taux de DFGe présentent un risque élevé d'hyperkaliémie initiale et récurrente.

Cannabis and Cigarette Use Before and After Living Kidney Donation.

BACKGROUND: It is unclear whether kidney donation leads to lifestyle changes in terms of cannabis and cigarette use. OBJECTIVE: To describe cigarette and cannabis use before and after kidney donation and to determine their associations with lifestyle and clinical factors. DESIGN: Retrospective cohort study. SETTING: The Living Kidney Donor program in the Champlain Local Health Integration Network at The Ottawa Hospital in Ottawa, Canada. PATIENTS: The study included 178 living kidney donors who donated between January 2009 and December 2018. MEASUREMENTS: Donors were screened for cannabis and cigarette use by telephone interview. Their clinical characteristics and changes in kidney function before and after donation were recorded. METHODS: Cannabis and cigarette use before and after kidney donation were compared using chi-square test. Risk factors associated with their use was examined by univariate and multivariate logistic regression. Wilcoxon rank sum test was used to examine the association of cannabis and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) estimated glomerular filtration rate (eGFR) at donation and at last follow-up. T-test was used to examine the association of cigarette smoking and CKD-EPI eGFR at donation and at last follow-up. RESULTS: Among 305 donors, 262 met inclusion criteria and 178 participated (mean of 4.7 ± 2.9 years from kidney donation). Cannabis and cigarette use were reported by 5% (9 of 178) and 13% (23 of 178) at donation. After donation, 8% (14 of 178) and 5% (9 of 178) started cannabis and cigarettes, respectively; 74% (17 of 23) of smokers remained smokers after donation and 88% (53 of 60) who quit smoking before donation did not restart after donation. In multivariate analysis, non-married/common-in-law status was associated with cannabis use (odds ratio, 2.73; 95% confidence interval, 1.05-7.11; P = .04). There was no difference in eGFR pre- or post-donation among cannabis or cigarette users. LIMITATIONS: The single-center study design limits generalizability. Social desirability bias may have affected survey responses and cigarette smoking was not quantified. CONCLUSIONS: Cannabis and cigarette use was uncommon in the studied population and was not associated with remaining kidney function. Cannabis use increased post-donation. Most smokers remained smokers after donation and most donors who quit smoking before donation did not restart after donation. This warrants education and support for potential donors who smoke, to quit smoking prior to donation to reduce risks of cardiovascular and end-stage kidney disease. TRIAL REGISTRATION: Not applicable as this is not a clinical trial.

CONTEXTE: On ignore si la perspective de faire don d'un rein conduit les donneurs potentiels à changer leurs habitudes de vie en matière de tabagisme et de consommation de cannabis. OBJECTIFS: Examiner la prévalence du tabagisme et de la consommation de cannabis avant et après le don d'un rein, puis déterminer leur association avec le mode de vie et les facteurs cliniques. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Le program de don de rein vivant du Réseau local d'intégration des services de santé de Champlain de l'hôpital d'Ottawa (Canada). SUJETS: L'étude a inclus 178 individus ayant fait don d'un rein entre janvier 2009 et décembre 2018. MESURES: Les donneurs ont été questionnés par téléphone sur leur consommation de cigarettes et de cannabis. Les caractéristiques cliniques et les changements dans la fonction rénale ont été enregistrés pré- et post-don. MÉTHODOLOGIE: Le test du Chi2 a été employé pour comparer la consommation de cigarettes et de cannabis pré- et post-don, tandis que les facteurs de risque associés à leur utilization ont été examinés par régression logistique univariée et multivariée. L'association entre la consommation de cannabis/le tabagisme et le CKD-EPI eGFR (débit de filtration glomérulaire estimé [DFGe] par l'équation de la Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration) a été examinée au moment du don et lors du dernier suivi par le test Wilcoxon (cannabis) ou le test t (tabagisme), selon le cas. RÉSULTATS: Des 305 donneurs admissibles, 262 répondaient aux critères d'inclusion et 178 ont participé à l'étude (moyenne: 4,7 ± 2,9 ans depuis le don). Au moment du don, 5 % (9/178) des donneurs consommaient du cannabis et 13 % (23/178) fumaient la cigarette. Après le don, 8 % (14/178) des donneurs ont commencé à consommer du cannabis et 5 % (9/178) à fumer la cigarette. La majorité des donneurs qui fumaient avant le don ont continué après le don (74 % [17/23]). La grande majorité des donneurs qui avaient cessé de fumer avant le don n'ont pas repris après (88 % [53/60]). Dans l'analyze multivariée, le fait de ne pas être marié ou conjoint de fait a été associé à la consommation de cannabis (rapport de cotes: 2,73; IC à 95 %: 1,05-7,11; p=0,04). Aucune différence n'a été observée dans les taux de filtration glomérulaire estimé pré- et post-don chez les fumeurs et les consommateurs de cannabis. LIMITES: L'étude est monocentrique, ce qui limite la généralisabilité des résultats. Un biais de désirabilité sociale pourrait avoir influé sur les réponses à l'enquête. Le tabagisme n'a pas été quantifié. CONCLUSION: Le tabagisme et la consommation de cannabis étaient peu courants dans la population étudiée; ces habitudes de vie n'ont pas été associées à la fonction rénale résiduelle. La consommation de cannabis a augmenté après le don. La plupart des fumeurs le sont demeurés après le don et la majorité des donneurs qui avaient cessé de fumer avant le don n'ont pas repris après. Ces résultats justifient de sensibiliser les donneurs potentiels à l'importance de cesser de fumer avant le don, et de les appuyer dans cette démarche, afin de réduire les risques de maladies cardiovasculaires et d'insuffisance rénale terminale.

A living donor kidney transplant recipient with mycobacterium senegalense bacteremia: A case report.

Mycobacterium senegalense is primarily known in sub-Saharan Africa to cause bovine farcy, a chronic granulomatous inflammation of the skin and lymphatics in cows. Reports of M. senegalense are rare among humans. We report a unique case of M. senegalense bloodstream infection in a living donor kidney transplant recipient with multiple possible sources of infection.

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVES: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. EXPOSURES: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. OUTCOMES: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. ANALYTICAL APPROACH: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. RESULTS: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. LIMITATIONS: Observational design, BP measurement data unavailable. CONCLUSIONS: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

Technique Survival and Determinants of Technique Failure in In-Center Nocturnal Hemodialysis: A Retrospective Observational Study.

BACKGROUND: Long-duration (7-8 hours) hemodialysis provides benefits compared with conventional thrice-weekly, 4-hour sessions. Nurse-administered, in-center nocturnal hemodialysis (INHD) may expand the population to whom an intensive dialysis schedule can be offered. OBJECTIVE: The primary objective of this study was to determine predictors of INHD technique failure, disruptions, and technique survival. DESIGN: This study used retrospective chart and database review methodology. SETTING: This study was conducted at a single Canadian INHD program operating in Victoria, British Columbia, within a tertiary care hospital. Our program serves a catchment population of approximately 450 000 people. PATIENTS/SAMPLE/PARTICIPANTS: Forty-three consecutive incident INHD patients took part in the INHD program of whom 42 provided informed consent to participate in this study. METHODS: We conducted a retrospective observational study including incident INHD patients from 2015 to 2017. The primary outcome was technique failure ≤6 months (TF ≤6). Secondary outcomes included technique survival and reasons for/predictors of INHD discontinuation or temporary disruption. Predictors of each outcome included demographics, comorbidities, and Clinical Frailty Scale (CFS) scoring. RESULTS: Among 42 patients, mean (SD) age, dialysis vintage, CFS score, and follow-up were 63 (16) years, 46 (55) months, 4 (1), and 11 (9) months, respectively. 52% were aged ≥65 years. TF ≤6 occurred in 12 (29%) patients. One-year technique survival censored for transplants and home dialysis transitions was 60%. Discontinuation related to insomnia (32%), medical status change (27%), and vascular access (23%). In unadjusted Cox survival analysis, 1-point increases in CFS score associated with a higher risk of technique failure (hazard ratio: 2.04, 95% confidence interval [CI]: 1.26-3.31). In an adjusted analysis, higher frailty severity also associated with temporary INHD disruptions (incidence rate ratio: 2.64, 95% CI: 1.55-4.50, comparing CFS of ≥4 to 1-3). LIMITATIONS: The retrospective, observational design of this study resulted in limited ability to control for confounding factors. In addition, the relatively small number of events observed owing to a small sample size diminished statistical power to inform study conclusions. Use of a single physician to determine the clinical frailty score is another limitation. Finally, the use of a single center for this study limits generalizability to other programs and clinic settings. CONCLUSIONS: INHD is a sustainable modality, even among older patients. Higher frailty associates with INHD technique failure and greater missed treatments. Inclusion of a CFS threshold of ≤4 into INHD inclusion criteria may help to identify individuals most likely to realize the long-term benefits of INHD. TRIAL REGISTRATION: Due to the retrospective and observational design of this study, trial registration was not necessary.

CONTEXTE: L'hémodialyse prolongée (7-8 heures) offre des avantages comparativement aux séances habituelles de quatre heures, administrées trois fois par semaine. L'hémodialyse nocturne en centre (HDNC), administrée par une infirmière, pourrait permettre de proposer un programme de dialyse prolongée à davantage de patients. OBJECTIF: L'étude visait principalement à déterminer les prédicteurs de l'échec, de l'interruption temporaire ou du succès de la modalité HDNC. TYPE D'ÉTUDE: Une méthodologie rétrospective a été employée pour examiner les dossiers médicaux et bases de données. CADRE: Étude menée dans le seul programme canadien d'HDNC, soit celui du centre de soins tertiaires de Victoria, en Colombie-Britannique. Ce programme dessert un bassin d'environ 450 000 personnes. SUJETS: Un total de 43 patients incidents consécutifs ont pris part au programme d'HDNC; 42 ont donné leur consentement éclairé pour participer à l'étude. MÉTHODOLOGIE: Nous avons procédé à une étude observationnelle rétrospective examinant les résultats de patients incidents sous HDNC entre 2015 et 2017. L'échec de la modalité dans les six premiers mois constituait l'issue principale. La réussite de la modalité et les prédicteurs d'une interruption temporaire ou complète de l'HDNC constituaient les issues secondaires. Les prédicteurs pour chaque résultat incluaient les données démographiques, les maladies concomitantes et le score sur l'échelle CFS (Clinical Frailty Scale) mesurant la fragilité clinique. RÉSULTATS: L'étude porte sur 42 sujets dont l'âge moyen s'établissait à 63 ans (ET: 16 ans); 52 % étaient âgés de 65 ans et plus. En moyenne, les patients étaient dialysés depuis 46 (55) mois, suivis depuis 11 (9) mois et présentaient un score CFS de 4 (1). L'échec de la modalité est survenu dans les six premiers mois pour 12 patients (29 %). La réussite de la modalité après 1 an, censurée pour les transplantations et les transitions vers la dialyse à domicile, était de 60 %. Les interruptions étaient liées à l'insomnie (32 %), au changement de statut médical (27 %) et à l'accès vasculaire (23 %). Dans l'analyse de survie de Cox non corrigée, des augmentations d'un point au score CFS étaient associées à un plus grand risque d'échec (RR: 2,04; IC à 95 %: 1,26-3,31). Dans l'analyse corrigée, l'augmentation de la fragilité a également été associée à une interruption temporaire de l'HDNC (rapport du taux d'incidence: 2,64; IC à 95 %: 1,55-4,50; comparaison d'un score CFS entre 1 et 3 à un score CFS égal ou supérieur à 4). LIMITES: La conception rétrospective et observationnelle de l'étude a limité le contrôle des facteurs confusionnels. De plus, le nombre relativement faible d'événements observés (échantillon de petite taille) a diminué la puissance statistique permettant d'étayer les conclusions. Enfin, l'étude est monocentrique, ce qui limite sa généralisabilité à d'autres programmes et contextes cliniques, et un seul médecin a déterminé les scores de fragilité clinique. CONCLUSION: L'HDNC s'avère une modalité viable, même pour les patients plus âgés. L'accroissement de la fragilité a été associé à un risque accru d'échec de la modalité et à davantage de traitements manqués. L'ajout d'un seuil de fragilité clinique (score ≤ 4) aux critères d'inclusion pour l'HDNC pourrait aider à identifier les personnes les plus susceptibles de profiter des avantages à long terme de cette modalité. ENREGISTREMENT DE L'ESSAI: Non nécessaire puisqu'il s'agit d'une étude rétrospective et observationnelle.

Performance of the Kidney Failure Risk Equation by Disease Etiology in Advanced CKD.

BACKGROUND AND OBJECTIVES: The kidney failure risk equation is a clinical tool commonly used for prediction of progression from CKD to kidney failure. The kidney failure risk equation's accuracy in advanced CKD and whether this varies by CKD etiology remains unknown. This study examined the kidney failure risk equation's discrimination and calibration at 2 and 5 years among a large tertiary care population with advanced CKD from heterogeneous etiologies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 1293 patients with advanced CKD (median eGFR 15 ml/min per 1.73 m2) referred to the Ottawa Hospital Multi-Care Kidney Clinic between 2010 and 2016, with follow-up clinical data available through 2018. Four-variable kidney failure risk equation scores for 2- and 5-year risks of progression to kidney failure (defined as dialysis or kidney transplantation) were calculated upon initial referral and correlated with the subsequent observed kidney failure incidence within these time frames. Receiver operating characteristic curves and calibration plots were used to measure the discrimination and calibration of the kidney failure risk equation both in the overall advanced CKD population and by CKD etiology: diabetic kidney disease, hypertensive nephrosclerosis, GN, polycystic kidney disease, and other. Pairwise comparisons of the receiver operating characteristic curves by CKD etiology were performed to compare kidney failure risk equation discrimination. RESULTS: The kidney failure risk equation provided adequate to excellent discrimination in identifying patients with CKD likely to progress to kidney failure at the 2- and 5-year time points both overall (2-year area under the curve, 0.83; 95% confidence interval, 0.81 to 0.85; 5-year area under the curve, 0.81; 95% confidence interval, 0.77 to 0.84) and across CKD etiologies. The kidney failure risk equation displayed adequate calibration at the 2- and 5-year time points both overall and across CKD etiologies (Hosmer-Lemeshow P≥0.05); however, the predicted risks of kidney failure were higher than the observed risks across CKD etiologies with the exception of polycystic kidney disease. CONCLUSIONS: The kidney failure risk equation provides adequate discrimination and calibration in advanced CKD and across CKD etiologies.

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

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

Safety and Efficacy of Tinzaparin Anticoagulation during Nocturnal Hemodialysis.

BACKGROUND: The safety and efficacy of low-molecular-weight heparin in the prevention of extracorporeal dialysis circuit clotting among in-center extended duration nocturnal hemodialysis (INHD) patients are unknown. The aim of this study was to determine the safety and efficacy of 2 doses of tinzaparin, among INHD patients receiving 6-8 h hemodialysis, 3 times per week. METHODS: We conducted a retrospective cohort study to examine antifactor Xa levels at time 0, 2 h, 4 h mid-hemodialysis (mid-HD), 6 h, and at end of each INHD session for 4 weeks and to determine extracorporeal dialysis circuit clotting and bleeding events after switching from unfractionated heparin to tinzaparin, using a standard protocol of tinzaparin delivery at the initiation and midpoint of HD. RESULTS: All 16 patients in The Ottawa Hospital INHD program were converted to tinzaparin and followed for 177 INHD sessions. Mean antifactor Xa level at 2 h of HD was 0.41 ± 0.21 (SD) IU/mL, at 4 h (mid-HD) 0.19 ± 0.17 IU/mL, at 6 h 0.44 ± 0.21 IU/mL, and at dialysis end 0.26 ± 0.14 IU/mL. Antifactor Xa levels were undetectable at the start of INHD, suggesting no tinzaparin accumulation. Five patients required an increase in tinzaparin due to extracorporeal dialysis circuit clotting. There were no bleeding events. One patient required a switch to fondaparinux due to an adverse reaction. CONCLUSION: Tinzaparin was safe and efficacious for most INHD patients without accumulation or bleeding. The conversion from unfractionated heparin to tinzaparin required an increased tinzaparin dose for 31% of INHD patients.

Alpha-Blocker Use and the Risk of Hypotension and Hypotension-Related Clinical Events in Women of Advanced Age.

Alpha-blockers (ABs) are commonly prescribed as part of a multidrug regimen in the management of hypertension. We set out to assess the risk of hypotension and related adverse events with AB use compared with other blood pressure (BP) lowering drugs using a population-based, retrospective cohort study of women (≥66 years) between 1995 and 2015 in Ontario, Canada. Cox proportional hazards examined the association of AB use and hypotension and related events (syncope, fall, and fracture) compared with other BP lowering drugs matched via a high dimensional propensity score. The primary outcome was a composite of hospitalizations for hypotension and related events (syncope, fractures, and falls) within 1 year. From 734 907 eligible women, 14 106 were dispensed an AB (mean age, 75.7; standard deviation 6.9 years, median follow-up 1 year) and matched to 14 106 dispensed other BP lowering agents. The crude incidence rate of hypotension and related events was 95.7 (95% CI [confidence interval], 90.4-101.1, events 1214 [8.6%]) with AB and 79.8 (95% CI, 74.9-84.7 per 1000 person-years, events 1025 [7.3%]) with other BP lowering medications (incident rate ratio, 1.20; 95% CI, 1.10-1.30). The risk was higher for hypotension (hazard ratio, 1.71; 95% CI, 1.33-2.20) and syncope (hazard ratio, 1.44; 95% CI, 1.18-1.75) with no difference in falls, fractures, adverse cardiac events, or all-cause mortality. Treatment of hypertension in women with ABs is associated with a higher risk of hypotension and hypotension-related events compared with other BP lowering agents. Our findings suggest that ABs should be used with caution, even as add on therapy for hypertension.