COVID-19 in chronic hemodialysis patients: A report of 9 cases in Madrid, Spain.

INTRODUCTION: In December 2019, a new respiratory disease, named COVID-19, caused by a novel coronavirus, emerged in Wuhan and since then spread rapidly throughout China and worldwide. Hemodialysis patients are an especially vulnerable subgroup of the general population. However, there are only a few reports on the course of COVID-19 in maintenance hemodialysis patients. CASE REPORT: We describe in depth the clinical, analytical, and radiological details of 9 hemodialysis patients from a single center in Madrid (Spain) diagnosed with COVID-19. Furthermore, we describe and discuss the therapeutic aspects and the patients' outcomes. DISCUSSION: We present one of the first case series of chronic hemodialysis patients with COVID-19. Between March 14 and April 8, 2020, out of 76 prevalent patients in our hemodialysis unit, 9 (11.8%) patients were diagnosed with COVID-19. The most common symptoms were fever (77.8%), asthenia (77.8%), cough (55.6%), and dyspnea (33.3%). A total of 3 patients developed severe pneumonia, whereas 4 patients developed mild pneumonia. In 2 patients, no pathologic changes were found on chest radiography. All patients presented lymphopenia. While 6 (66.7%) patients required hospitalization, none of them was admitted to intensive care unit. The most common treatments used were azithromycin (100%), hydroxychloroquine (66.7%), lopinavir/ritonavir (55.6%) and ß-interferon (22.2%). In general, we observed a mild to moderate severity of disease in our case series. One patient died, however due to a cause not related to COVID-19.

Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells.

There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity.

Effect of hyperchloremia on acute kidney injury in critically ill septic patients: a retrospective cohort study.

BACKGROUND: Hyperchloremia is common in critically ill septic patients. The impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not well studied. We investigated the association between hyperchloremia and AKI within the first 72 h of intensive care unit (ICU) admission. METHODS: 6490 ICU adult patients admitted with severe sepsis or septic shock were screened for eligibility. Exclusion criteria included: AKI on admission, baseline estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, chronic renal replacement therapy, absent baseline serum creatinine data, and absent serum chloride data on ICU admission. RESULTS: A total of 1045 patients were available for analysis following the implementation of eligibility criteria: 303 (29%) had hyperchloremia (Cl0 ≥ 110 mEq/L) on ICU admission, 561 (54%) were normochloremic (Cl0 101-109 mEq/L) and 181 (17%) were hypochloremic (Cl0 ≤ 100 mEq/L). AKI within the first 72 h of ICU stay was the dependent variable. Chloride on ICU admission (Cl0) and change in Cl by 72 h (ΔCl = Cl72 - Cl0) were the independent variables. The odds for AKI were not different in the hyperchloremic group when compared to the normochloremic group [adjusted odds ratio (OR) =0.80, 95% confidence interval [CI] (0.51-1.25); p = 0.33] after adjusting for demographics, comorbidities, baseline kidney function, drug exposure and critical illness indicators including cumulative fluid balance and base deficit. Furthermore, within the subgroup of patients with hyperchloremia on ICU admission, neither Cl0 nor ΔCl was associated with AKI or with moderate/severe AKI (KDIGO Stage ≥2). CONCLUSIONS: Hyperchloremia occurs commonly among critically ill septic patients admitted to the ICU, but does not appear to be associated with an increased risk for AKI within the first 72 h of admission.

Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease.

OBJECTIVE: Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. DESIGN: Retrospective cohort study. SETTING: Urban academic medical center ICU. PATIENTS: ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury-/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease-; and 1.5 L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury. CONCLUSIONS: Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients.

OBJECTIVES: Hyperchloremia is frequently observed in critically ill patients in the ICU. Our study aimed to examine the association of serum chloride (Cl) levels with hospital mortality in septic ICU patients. DESIGN: Retrospective cohort study. SETTING: Urban academic medical center ICU. PATIENTS: ICU adult patients with severe sepsis or septic shock who had Cl measured on ICU admission were included. Those with baseline estimated glomerular filtration rate less than 15 mL/min/1.73 m or chronic dialysis were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,940 patients included in the study, 615 patients (31.7%) had hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission. All-cause hospital mortality was the dependent variable. Cl on ICU admission (Cl0), Cl at 72 hours (Cl72), and delta Cl (ΔCl = Cl72 - Cl0) were the independent variables. Those with Cl0 greater than or equal to 110 mEq/L were older and had higher cumulative fluid balance, base deficit, and Sequential Organ Failure Assessment scores. Multivariate analysis showed that higher Cl72 but not Cl0 was independently associated with hospital mortality in the subgroup of patients with hyperchloremia on ICU admission (adjusted odds ratio for Cl72 per 5 mEq/L increase = 1.27; 95% CI, 1.02-1.59; p = 0.03). For those who were hyperchloremic on ICU admission, every within-subject 5 mEq/L increment in Cl72 was independently associated with hospital mortality (adjusted odds ratio for ΔCl 5 mEq/L = 1.37; 95% CI, 1.11-1.69; p = 0.003). CONCLUSIONS: In critically ill septic patients manifesting hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission, higher Cl levels and within-subject worsening hyperchloremia at 72 hours of ICU stay were associated with all-cause hospital mortality. These associations were independent of base deficit, cumulative fluid balance, acute kidney injury, and other critical illness parameters.

Effect of ezetimibe on major atherosclerotic disease events and all-cause mortality.

Despite ezetimibe's ability to reduce serum cholesterol levels, there are concerns over its vascular effects and whether it prevents or ameliorates atherosclerotic disease (AD). The aims of this study were to estimate the effect of ezetimibe use on major AD events and all-cause mortality and to compare these associations to those observed for hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use. A total of 367 new ezetimibe users were identified from November 1, 2002, to December 31, 2009. These subjects were aged ≥18 years and had no previous statin use. One to 4 statin user matches were identified for each ezetimibe user, resulting in a total of 1,238 closely matched statin users. Pharmacy data and drug dosage information were used to estimate a moving window of ezetimibe and statin exposure for each day of study follow-up. The primary outcome was a composite of major AD events (coronary heart disease, cerebrovascular disease, and peripheral vascular disease events) and all-cause death. Ezetimibe use (odds ratio 0.33, 95% confidence interval 0.13 to 0.86) and statin use (odds ratio 0.61, 95% confidence interval 0.36 to 1.04) were associated with reductions in the likelihood of the composite outcome. These protective associations were most significant for cerebrovascular disease events and all-cause death. Subgroup analyses by gender, race or ethnicity, history of AD, diabetes status, and estimated renal function showed consistent estimates across strata, with no significant differences between ezetimibe and statin use. In conclusion, ezetimibe appeared to have a protective effect on major AD events and all-cause death that was not significantly different from that observed for statin use.