Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study.

CONTEXT: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. OBJECTIVE: To investigate the associations of aldosterone and renin with body composition according to sex in the general population. DESIGN: Population-based cohort study. SETTING: Québec (Canada). PARTICIPANTS: Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687). EXPOSURES: Plasma aldosterone and renin concentrations. MAIN OUTCOME MEASURES: Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). RESULTS: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (p<0.05). Aldosterone (p=0.02), but not renin (p=0.43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (p<0.05), but not aldosterone (p≥0.05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (p<0.05) but were not associated with lean body mass or muscle mass (p≥0.05). All aforementioned associations were independent of body weight. CONCLUSIONS: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Impact of electrolyte abnormalities and adverse outcomes in persons with eating disorders: A systematic review protocol.

BACKGROUND: Electrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders. METHODS: A systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted. DISCUSSION: This review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study. DISSEMINATION: The final manuscript will be submitted for publication in a journal. REVIEW REGISTRATION: This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497.

Kidney complications of Wilson disease and its treatments: A case report and literature review.

Wilson disease is a rare autosomal recessive genetic disorder of copper metabolism that leads to copper accumulation and subsequent organ dysfunction. While classically considered a condition that primarily affects the liver and nervous system, Wilson disease and its treatments can also result in a wide range of kidney complications as well. We present the case of a 31-year-old female with a longstanding (> 10 year) history of Wilson disease who developed acute-onset nephrotic syndrome including heavy proteinuria, hypoalbuminemia, and edema after being transitioned from zinc to D-penicillamine for copper chelation therapy. Following simple cessation of D-penicillamine (and without any immunosuppressive therapies including corticosteroids), the nephrotic syndrome showed remarkable improvement including complete remission within several months. This review comprehensively summarizes the kidney complications associated with Wilson disease and its treatments.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

BACKGROUND AND HYPOTHESIS: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. METHODS: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. RESULTS: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. CONCLUSIONS: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study.

BACKGROUND: Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management. OBJECTIVE: To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era. METHODS: Design: Retrospective population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017. EXPOSURE: Sex (female vs. male). OUTCOMES AND MEASURES: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression. RESULTS: Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997]). CONCLUSIONS: Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.

Comparison of eGFR Equations to Guide Dosing of Medications for Kidney Transplant Recipients.

BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

Comparison of ß-blocker agents and mortality in maintenance hemodialysis patients: an international cohort study.

Background: Despite a lack of clinical trial data, ß-blockers are widely prescribed to dialysis patients. Whether specific ß-blocker agents are associated with improved long-term outcomes compared with alternative ß-blocker agents in the dialysis population remains uncertain. Methods: We analyzed data from an international cohort study of 10 125 patients on maintenance hemodialysis across 18 countries that were newly prescribed a ß-blocker medication within the Dialysis Outcomes and Practice Patterns Study (DOPPS). The following ß-blocker agents were compared: metoprolol, atenolol, bisoprolol and carvedilol. Multivariable Cox proportional hazards models were used to estimate the association between the newly prescribed ß-blocker agent and all-cause mortality. Stratified analyses were performed on patients with and without a prior history of cardiovascular disease. Results: The mean (standard deviation) age in the cohort was 63 (15) years and 57% of participants were male. The most commonly prescribed ß-blocker agent was metoprolol (49%), followed by carvedilol (29%), atenolol (11%) and bisoprolol (11%). Compared with metoprolol, atenolol {adjusted hazard ratio (HR) 0.77 [95% confidence interval (CI) 0.65-0.90]} was associated with a lower mortality risk. There was no difference in mortality risk with bisoprolol [adjusted HR 0.99 (95% CI 0.82-1.20)] or carvedilol [adjusted HR 0.95 (95% CI 0.82-1.09)] compared with metoprolol. These results were consistent upon stratification of patients by presence or absence of a prior history of cardiovascular disease. Conclusions: Among patients on maintenance hemodialysis who were newly prescribed ß-blocker medications, atenolol was associated with the lowest mortality risk compared with alternative agents.

Effect and outcome of equity, diversity and inclusion programs in healthcare institutions: a systematic review protocol.

BACKGROUND: Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients' viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions. METHODS: We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation. ANTICIPATED RESULTS: We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions. ETHICS AND DISSEMINATION: No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice. REVIEW REGISTRATION: This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

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.

Social determinants of health and dialysis modality selection in patients with advanced chronic kidney disease: A retrospective cohort study.

BACKGROUND: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood. METHODS: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation. RESULTS: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m2, respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78)). CONCLUSIONS: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure.

Has the time come for age-adapted glomerular filtration rate criteria to define chronic kidney disease: how soon is now?

PURPOSE OF REVIEW: The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m 2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age. RECENT FINDINGS: The fixed eGFR threshold of <60 ml/min/1.73 m 2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults. SUMMARY: To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach.