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BACKGROUND: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease (CKD). We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5. METHODS: A Medline search from inception to November 2022 was conducted to identify randomised controlled trials (RCTs) in patients with CKD stage 4-5 (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) comparing RAAS blockade vs placebo or alternative antihypertensive therapy. Different intervention strategies were assessed (RAAS use vs nonuse, initiation vs placebo/alternative therapy, or discontinuation vs continuation). The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). The risk ratio (RR) was estimated with the use of a random-effects model. RESULTS: Nine RCTs (1150 patients) were included. RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74-0.96; P = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63-1.65; P = 0.93) and RR 0.87 (95% CI 0.49-1.57; P = 0.65), respectively. CONCLUSIONS: RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD.
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Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. Sources of information: We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. Methods: From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooled r correlation coefficient of .57 and .36, respectively. Among echocardiographic parameters, left ventricular ejection fraction and inferior vena cava index had the strongest correlation with the number of B-lines, with a pooled r coefficient of .35 and .31, respectively. Three randomized studies compared a lung ultrasound-guided approach with standard of care on hard clinical endpoints. Although patients in the lung ultrasound group achieved better decongestion and blood pressure control, there was no difference between the 2 management strategies with respect to death from any cause or major adverse cardiovascular events. Key findings: Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. Limitations: The included studies were heterogeneous and of relatively limited quality.
Motif de la revue: L'échographie pulmonaire est une technique non-invasive réalisée au chevet du patient qui permet d'évaluer avec précision la congestion pulmonaire en mesurant l'eau pulmonaire extravasculaire. Cette technique facilement accessible est de plus en plus utilisée. Notre principal critère de jugement était de comparer l'efficacité de l'évaluation de la volémie par échographie pulmonaire avec l'évaluation clinique, l'échocardiographie, la bio-impédance ou les biomarqueurs. Les critères d'évaluation secondaires étaient la mortalité toutes causes confondues et les événements cardiovasculaires. Sources: Nous avons recherché sur MEDLINE les études observationnelles et les essais randomisés où une échographie pulmonaire avait été réalisée chez des patients sous dialyse d'entretien. Méthodologie: Sur un total de 2 363 articles, nous avons retenu 28 études (25 observationnelles et 3 randomisées). Les coefficients de corrélation ont été regroupés pour chaque variable d'intérêt en utilisant la méthode générique de variance inverse avec un modèle à effets aléatoires. Les paramètres cliniques qui avaient montré les corrélations les plus élevées avec le nombre de lignes B à l'échographie étaient le statut de l'insuffisance cardiaque selon la classification de la New York Heart Association et l'auscultation pulmonaire, avec des coefficients de corrélation r regroupés respectifs de 0,57 et de 0,36. Les paramètres de l'échocardiographie qui avaient montré les plus fortes corrélations avec le nombre de lignes B étaient la fraction d'éjection du ventricule gauche et l'indice de la veine cave inférieure, avec des coefficients r regroupés respectifs de 0,35 et de 0,31. Trois essais randomisés avaient comparé une approche guidée par échographie pulmonaire aux normes de soins selon des critères cliniques stricts. Bien que les patients du groupe avec échographie pulmonaire aient montré une décongestion plus efficace et un meilleur contrôle de la pression artérielle, aucune différence n'a été observée entre les deux stratégies de prise en charge en ce qui concerne les décès de toutes causes confondues ou les événements cardiovasculaires indésirables majeurs. Principales observations: L'échographie pulmonaire pourrait être envisagée pour identifier les patients qui présentent une surcharge volumique subclinique. Les essais inclus n'ont pas montré de différences dans les résultats cliniquement pertinents. Le nombre d'études incluses était faible et plusieurs étaient de qualité sous-optimale. Limites: Les études incluses étaient hétérogènes et de qualité relativement limitée.
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Background: Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19. Methods: Retrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without. Results: Patients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation. Conclusions: Older adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.
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CONTEXT: Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. METHODS: We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. FINDINGS: Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). CONCLUSION: No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.
