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2.
Circulation ; 149(8): e347-e913, 2024 02 20.
Article in English | MEDLINE | ID: mdl-38264914

ABSTRACT

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.


Subject(s)
Cardiovascular Diseases , Heart Diseases , Stroke , Humans , United States/epidemiology , American Heart Association , Heart Diseases/epidemiology , Stroke/epidemiology , Stroke/prevention & control , Obesity/epidemiology
4.
Am J Hypertens ; 37(2): 91-100, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-37772757

ABSTRACT

Hypertension is the single most important and modifiable risk factor for cardiovascular morbidity and mortality worldwide. Non pharmacologic interventions, in particular dietary modifications have been established to decrease blood pressure (BP) and hypertension related adverse cardiovascular events. Among those dietary modifications, sodium intake restriction dominates guidelines from professional organizations and has garnered the greatest attention from the mainstream media. Despite guidelines and media exhortations, dietary sodium intake globally has not noticeably changed over recent decades. Meanwhile, increasing dietary potassium intake has remained on the sidelines, despite similar BP-lowering effects. New research reveals a potential mechanism of action, with the elucidation of its effect on natriuresis via the potassium switch effect. Additionally, potassium-substituted salt has been shown to not only reduce BP, but also reduce the risk for stroke and cardiovascular mortality. With these data, we argue that the focus on dietary modification should shift from a sodium-focused to a sodium- and potassium-focused approach with an emphasis on intervention strategies which can easily be implemented into clinical practice.


Subject(s)
Cardiovascular System , Hypertension , Humans , Potassium , Blood Pressure , Sodium , Potassium, Dietary
6.
Circulation ; 149(2): 124-134, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38031887

ABSTRACT

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.


Subject(s)
Cardiovascular Diseases , Hyperaldosteronism , Hypertension , Male , Humans , Adult , Middle Aged , Aged , Female , Aldosterone , Ventricular Remodeling , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/complications , Renin , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Prospective Studies , Cohort Studies , Pulse Wave Analysis , Hypertension/complications , Hyperaldosteronism/complications , Hyperaldosteronism/epidemiology , Heart Atria
7.
J Hypertens ; 42(1): 23-49, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37712135

ABSTRACT

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.


Subject(s)
Cardiovascular Diseases , Heart Failure , Hypertension , Humans , Hypertension/prevention & control , Hypertension/complications , Cardiovascular Diseases/etiology , Life Style , Blood Pressure , Heart Failure/complications
8.
Can J Kidney Health Dis ; 10: 20543581231215858, 2023.
Article in English | MEDLINE | ID: mdl-38033483

ABSTRACT

Background: Updates to the Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Vascular Access emphasize the "right access, in the right patient, at the right time, for the right reasons." Although this implies a collaborative approach, little is known about how patients, their caregivers, and health care providers engage in vascular access (VA) decision-making. Objective: To explore how the perspectives of patients receiving hemodialysis, their caregivers, and hemodialysis care team align and diverge in relation to VA selection. Design: Qualitative descriptive study. Setting: Five outpatient hemodialysis centers in Calgary, Alberta. Participants: Our purposive sample included 19 patients receiving maintenance hemodialysis, 2 caregivers, and 21 health care providers (7 hemodialysis nurses, 6 VA nurses, and 8 nephrologists). Methods: We conducted semi-structured interviews with consenting participants. Using an inductive thematic analysis approach, we coded transcripts in duplicate and characterized themes addressing our research objective. Results: While participants across roles shared some perspectives related to VA decision-making, we identified areas where views diverged. Areas of alignment included (1) optimizing patient preparedness-acknowledging decisional readiness and timing, and (2) value placed on trusting relationships with the kidney care team-respecting decisional autonomy with guidance. Perspectives diverged in the following aspects: (1) differing VA priorities and preferences-patients' emphasis on minimizing disruptions to normalcy contrasted with providers' preferences for fistulas and optimizing biomedical parameters of dialysis; (2) influence of personal and peer experience-patients preferred pragmatic, experiential knowledge, whereas providers emphasized informational credibility; and (3) endpoints for VA review-reassessment of VA decisions was prompted by access dissatisfaction for patients and a medical imperative to achieve a functioning access for health care providers. Limitations: Participation was limited to individuals comfortable communicating in English and from urban, in-center hemodialysis units. Few informal caregivers of people receiving hemodialysis and younger patients participated in this study. Conclusions: Although patients, caregivers, and healthcare providers share perspectives on important aspects of VA decisions, conflicting priorities and preferences may impact the decisional outcome. Findings highlight opportunities to bridge knowledge and readiness gaps and integrate shared decision-making in the VA selection process.


Contexte: Les mises à jour des lignes directrices de pratiques cliniques en matière d'accès vasculaire de la KDOQI (Kidney Disease Outcomes Quality Initiative) insistent sur la création « du bon accès, à la bonne personne, au bon moment et pour les bonnes raisons ¼. Ces recommandations sous-entendent une approche collaborative, mais la façon dont les patients, leurs soignants et les prestataires de soins de santé participent à la prise de décision sur l'accès vasculaire (AV) demeure mal connue. Objectif: Explorer les accords et les divergences dans les points de vue des patients sous hémodialyse, leurs soignants et leur équipe de soins relativement à la sélection de l'AV. Conception: Étude qualitative et descriptive. Cadre: Cinq centres d'hémodialyse ambulatoire à Calgary (Alberta). Sujets: Notre échantillon choisi à dessein était composé de 19 patients sous hémodialyse d'entretien, 2 soignants et 21 prestataires de soins de santé (7 infirmières en hémodialyse, 6 infirmières en AV et 8 néphrologues). Méthodologie: Nous avons mené des entrevues semi-structurées auprès des participants consentants. Une approche d'analyse thématique inductive a été employée pour coder les transcriptions en double et caractériser les thèmes répondant à l'objectif de recherche. Résultats: Certains points de vue sur la prise de décision en matière d'AV étaient partagés par tous les participants, mais nous avons identifié quelques domaines de divergence. Les participants s'entendaient sur : 1) l'optimisation de la préparation des patients ­ reconnaître l'état de préparation et le moment de prendre la décision; et 2) la valeur accordée aux relations de confiance avec l'équipe de soins rénaux ­ respecter l'autonomie décisionnelle après conseils. Les points de vue divergeaient sur : 1) les priorités et préférences à l'égard de l'AV ­ l'accent mis par les patients sur la minimisation des perturbations de la vie courante contrastait avec les préférences des prestataires de soins pour les fistules et l'optimisation des paramètres biomédicaux de la dialyse; 2) l'influence de l'expérience personnelle et des pairs ­ les patients préféraient des connaissances pragmatiques et expérientielles, tandis que les prestataires de soins mettaient l'accent sur la crédibilité de l'information; et 3) les critères d'évaluation de l'AV ­ la réévaluation du choix de l'AV est motivée par l'insatisfaction des patients à l'égard de l'accès et, du côté des prestataires de soins, par l'impératif médical de parvenir à un accès fonctionnel. Limites: Seules les personnes fréquentant une unité d'hémodialyse en centre urbain et à l'aise de communiquer en anglais ont pu participer. Les participants comptaient peu de patients plus jeunes et de soignants informels de personnes sous hémodialyse. Conclusion: Bien que les patients, les soignants et les prestataires de soins de santé s'entendent sur certains aspects importants de la décision concernant l'AV, celle-ci pourrait être influencée par des priorités et préférences contradictoires. Nos résultats mettent en évidence des occasions d'intégrer la prise de décision partagée dans le processus de sélection d'un AV et de combler les lacunes dans les connaissances et la préparation des patients.

10.
Pharmacotherapy ; 43(11): 1206-1220, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37596844

ABSTRACT

Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction were conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recommendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.


Subject(s)
Anti-Infective Agents , Intermittent Renal Replacement Therapy , Humans , Adult , Critical Illness/therapy , Anti-Bacterial Agents , Vancomycin/pharmacokinetics , Renal Replacement Therapy
11.
J Clin Invest ; 133(13)2023 07 03.
Article in English | MEDLINE | ID: mdl-37395275

ABSTRACT

The field of nephrology has been slow in moving beyond the utilization of creatinine as an indicator for chronic kidney disease and acute kidney injury (AKI). Early diagnosis and establishment of etiology, in particular, are important for treatment of AKI. In the setting of hospital-acquired AKI, tubular injury is more common, but acute interstitial nephritis (AIN) has a more treatable etiology. However, it is likely that AIN is under- or misdiagnosed due to current strategies that largely rely on clinical gestalt. In this issue of the JCI, Moledina and colleagues made an elegant case for the chemokine called C-X-C motif ligand 9 (CXCL9) as a biomarker of AIN. The authors used urine proteomics and tissue transcriptomics in patients with and without AIN to identify CXCL9 as a promising, noninvasive, diagnostic biomarker of AIN. These results have clinical implications that should catalyze future research and clinical trials in this space.


Subject(s)
Acute Kidney Injury , Nephritis, Interstitial , Humans , Nephritis, Interstitial/complications , Nephritis, Interstitial/diagnosis , Nephritis, Interstitial/drug therapy , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Biomarkers , Creatinine
12.
Intern Med J ; 53(10): 1739-1751, 2023 10.
Article in English | MEDLINE | ID: mdl-37493367

ABSTRACT

Resistant hypertension (RHT) is typically defined as blood pressure that remains above guideline-directed targets despite the use of three anti-hypertensives, usually including a diuretic, at optimal or maximally tolerated doses. It is generally estimated to affect 10-30% of those diagnosed with hypertension, though the true incidence might be lower after one factor in the prevalence of non-adherence. Risk factors for its development include diabetes, obesity and other adverse lifestyle factors, and a diagnosis of RHT confers a greater risk of adverse cardiovascular outcomes, such as stroke, heart failure and mortality. It is essential to exclude pseudoresistance and secondary hypertension and to ensure non-pharmacologic management is optimised prior to consideration of fourth-line anti-hypertensive agents or advanced interventions, such as device therapies. In this review, we will cover the different definitions of RHT, along with the importance of careful diagnosis and management strategies, and discuss newer agents and research needs.


Subject(s)
Hypertension , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Antihypertensive Agents/therapeutic use , Blood Pressure , Diuretics , Risk Factors
13.
Clin Toxicol (Phila) ; 61(5): 326-335, 2023 05.
Article in English | MEDLINE | ID: mdl-37293897

ABSTRACT

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.


Subject(s)
Ethylene Glycol , Kidney , Methanol , Poisoning , Adolescent , Adult , Female , Humans , 2-Propanol , Aftercare , Ethylene Glycol/poisoning , Ethylene Glycols , Methanol/poisoning , Observational Studies as Topic , Patient Discharge , Poisoning/therapy , Propylene Glycol , Retrospective Studies
14.
Am J Physiol Renal Physiol ; 325(1): F99-F104, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37262087

ABSTRACT

Hypertension is among the most prevalent medical conditions globally and a major contributor to chronic kidney disease, cardiovascular disease, and death. Prevention through nonpharmacological, population-level interventions is critically needed to halt this worldwide epidemic. However, there are ongoing disagreements as to where public policy efforts should focus. Recently the Salt Substitute and Stroke Study demonstrated the efficacy of substituting table salt with potassium salt to reduce the risk of stroke, major cardiovascular events, and death. However, this sparked debate over whether sodium or potassium should be prioritized in countries where table salt substitution was less feasible. In this commentary, we summarize arguments in favor of either strategy: reduced sodium or increased potassium intake. Moreover, we discuss evidence and policy approaches related to either or combined approaches relevant to cultural context. Ultimately, there is an urgent need for policies that both reduce sodium and increase potassium intake; however, identifying a strategy that fits cultural context will be key to improve population-wide blood pressures.


Subject(s)
Hypertension , Stroke , Humans , Potassium , Sodium , Sodium Chloride, Dietary/adverse effects , Blood Pressure/physiology , Hypertension/epidemiology , Hypertension/prevention & control , Stroke/epidemiology
17.
Article in English | MEDLINE | ID: mdl-37071648

ABSTRACT

BACKGROUND: For patients who initiate dialysis during a hospital admission and continue to require dialysis after discharge, outpatient dialysis management could be improved by better understanding the future likelihood of recovery to dialysis independence and the competing risk of death. METHODS: We derived and validated linked models to predict the subsequent recovery to dialysis independence and death within 1 year of hospital discharge using a population-based cohort of 7657 patients in Ontario, Canada. Predictive variables included age, comorbidities, length of hospital admission, intensive care status, discharge disposition, and prehospital admission eGFR and random urine albumin-to-creatinine ratio. Models were externally validated in 1503 contemporaneous patients from Alberta, Canada. Both models were created using proportional hazards survival analysis, with the "Recovery Model" using Fine-Gray methods. Probabilities generated from both models were used to develop 16 distinct "Recovery and Death in Outpatients" (ReDO) risk groups. RESULTS: ReDO risk groups in the derivation group had significantly distinct 1-year probabilities for recovery to dialysis independence (first quartile: 10% [95% confidence interval (CI), 9% to 11%]; fourth quartile: 73% [70% to 77%]) and for death (first quartile: 12% [11% to 13%]; fourth quartile: 46% [43% to 50%]). In the validation group, model discrimination was modest (c-statistics [95% CI] for recovery and for death quartiles were 0.70 [0.67 to 0.73] and 0.66 [0.62 to 0.69], respectively), but calibration was excellent (integrated calibration index [95% CI] was 7% [5% to 9%] and 4% [2% to 6%] for recovery and death, respectively). CONCLUSIONS: The ReDO models generated accurate expected probabilities of recovery to dialysis independence and death in patients who continued outpatient dialysis after initiating dialysis in hospital. An online tool on the basis of the models is available at https://qxmd.com/calculate/calculator_874 .

18.
Article in English | MEDLINE | ID: mdl-37099447

ABSTRACT

BACKGROUND: Nirmatrelvir/ritonavir has been shown to reduce the risk of COVID-19 related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program. METHODS: Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on Day 8) based on drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor level monitoring was implemented. Outcomes including tacrolimus level changes, serum creatinine and acute kidney injury (AKI, defined as serum creatinine increase by 30%) and clinical outcomes were described globally and compared between algorithms. RESULTS: Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first timepoint, 7 days after withholding of calcineurin inhibitor and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44(48%) and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 ug/L [4.0, 6.2] versus 4.8 ug/L [4.3, 5.7] p=0.70). There were no acute rejections or other complications. CONCLUSIONS: Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.

19.
Clin J Am Soc Nephrol ; 18(4): 485-490, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36723285

ABSTRACT

BACKGROUND: Nirmatrelvir/ritonavir was approved for use in high-risk outpatients with coronavirus disease 2019 (COVID-19). However, patients with severe CKD were excluded from the phase 3 trial, and the drug is not recommended for those with GFR <30 ml/min per 1.73 m 2 . On the basis of available pharmacological data, we developed a modified low-dose regimen of nirmatrelvir/ritonavir 300/100 mg on day 1, followed by 150/100 mg daily from day 2 to 5. In this study, we report our experience with this modified dose regimen in dialysis patients in the Canadian province of Ontario. METHODS: We included dialysis patients who developed COVID-19 and were treated with the modified dose nirmatrelvir/ritonavir regimen during a 60-day period between April 1 and May 31, 2022. Details of nirmatrelvir/ritonavir use and outcomes were captured manually, and demographic data were obtained from a provincial database. Data are presented with descriptive statistics. The principal outcomes we describe are 30-day hospitalization, 30-day mortality, and required medication changes with the modified dose regimen. RESULTS: A total of 134 dialysis patients with COVID-19 received nirmatrelvir/ritonavir during the period of study. Fifty-six percent were men, and the mean age was 64 years. Most common symptoms were cough and/or sore throat (60%). Medication interactions were common with calcium channel blockers, statins being the most frequent. Most patients (128, 96%) were able to complete the course of nirmatrelvir/ritonavir, and none of the patients who received nirmatrelvir/ritonavir died of COVID-19 in the 30 days of follow-up. CONCLUSIONS: A modified dose of nirmatrelvir/ritonavir use was found to be safe and well tolerated, with no serious adverse events being observed in a small sample of maintenance dialysis patients.


Subject(s)
COVID-19 , Renal Dialysis , Female , Humans , Male , Middle Aged , Antiviral Agents/adverse effects , COVID-19 Drug Treatment , Ontario , Outpatients , Ritonavir/adverse effects
20.
Can J Kidney Health Dis ; 10: 20543581231154183, 2023.
Article in English | MEDLINE | ID: mdl-36814964

ABSTRACT

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.


Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.

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