Association Between Hormone Replacement Therapy and Development of Endometrial Cancer: Results From a Prospective US Cohort Study

Although hormone replacement therapy (HRT) use is associated with elevated endometrial cancer(EC) risk, little evidence assesses potential effect-modifiers on HRT-related EC in a long-term follow-up. In this large-scale longitudinal cohort study, we tried to evaluate the association between different HRT types/methods use and risk of EC, and reveal this risk within different body mass index (BMI) groups. In whole cohort, 677 EC occurred during mean 11.6 years follow-up. Cox proportional hazards regression was used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs) with HRT status (never, former, or current) for risk of EC incidence. Current HRT use was not significantly associated with EC risk (HR for current vs. never HRT use: 1.13; 95% CI: 0.92, 1.38) in the whole cohort, but presented a dose-response effect on increased EC risk (HR for >10-year use vs. never HRT use: 1.73; 95% CI: 1.35, 2.21). Moreover, EC risk differed in distinct regimens or subsets (all Pinteraction < 0.05). Estrogen-only use was associated with elevated EC risk (HR for current vs. never HRT use: 1.51; 95% CI: 1.12, 2.04), but women with high BMI (> 30 kg/m2) who currently use estrogen-only harbored decreased EC risk (HR: 0.56; 95% CI: 0.38, 0.82) compared to counterparts without HRT use. Estrogen-only use is associated with increased EC risk, and precise monitoring of EC development for postmenopausal women with long-term HRT use are urgently needed. BMI could serve as an important surrogate to assess this risk.

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil

Introduction Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. Methods This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. Results The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. Conclusion AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

Mineralocorticoid Receptor Antagonist Use and Hard Renal Outcomes in Real-World Patients With Chronic Kidney Disease

Background: Real-world evidence about mineralocorticoid receptor antagonist (MRA) use has been limited in chronic kidney disease, particularly regarding its association with hard renal outcomes. Methods: In this retrospective cohort study, adult chronic kidney disease outpatients referred to the department of nephrology at an academic hospital between January 2005 and December 2018 were analyzed. The main inclusion criteria were estimated glomerular filtration rate ≥10 and <60 mL/min per 1.73 m 2 and follow-up ≥90 days. The exposure of interest was MRA use, defined as the administration of spironolactone, eplerenone, or potassium canrenoate. The primary outcome was renal replacement therapy initiation, defined as the initiation of chronic hemodialysis, peritoneal dialysis, or kidney transplantation. A marginal structural model using inverse probability of weighting was applied to account for potential time-varying confounders. Results: Among a total of 3195 patients, the median age and estimated glomerular filtration rate at baseline were 66 years and 38.4 mL/min per 1.73 m 2 , respectively. During follow-up (median, 5.9 years), 770 patients received MRAs, 211 died, and 478 started renal replacement therapy. In an inverse probability of weighting-weighted pooled logistic regression model, MRA use was significantly associated with a 28%-lower rate of renal replacement therapy initiation (hazard ratio, 0.72 [95% CI, 0.53–0.98]). The association between MRA use and renal replacement therapy initiation was dose-dependent ( P for trend <0.01) and consistent across patient subgroups. The incidence of hyperkalemia (>5.5 mEq/L) was somewhat higher in MRA users but not significant (hazard ratio, 1.14 [95% CI, 0.88–1.48]). Conclusions: MRA users showed a better renal prognosis across various chronic kidney disease subgroups in a real-world chronic kidney disease population.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients

Background: Acute kidney injury (AKI) is frequently associated with COVID–19 and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalized COVID–19 patients. Methods: This study is part of the multicentre cohort, the Brazilian COVID–19 Registry. A total of 5,212 adult COVID–19 patients were included between March/2020 and September/2020. We evaluated four categories of predictor variables: (1) demographic data; (2) comorbidities and conditions at admission; (3) laboratory exams within 24 h; and (4) the need for mechanical ventilation at any time during hospitalization. Variable selection was performed using generalized additive models (GAM) and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. The accuracy was assessed using the area under the receiver operating characteristic curve (AUCROC). Risk groups were proposed based on predicted probabilities: non-high (up to 14.9%), high (15.0 to 49.9%), and very high risk (≥ 50.0%). Results: The median age of the model–derivation cohort was 59 (IQR 47–70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalization. The validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in–hospital mortality. Thirty–two variables were tested and four important predictors of the need for KRT during hospitalization were identified using GAM: need for mechanical ventilation, male gender, higher creatinine at admission, and diabetes. The MMCD score had excellent discrimination in derivation (AUROC = 0.929; 95% CI 0.918–0.939) and validation (AUROC = 0.927; 95% CI 0.911–0.941) cohorts an good overall performance in both cohorts (Brier score: 0.057 and 0.056, respectively). The score is implemented in a freely available online risk calculator (https://www.mmcdscore.com/). Conclusion: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalized COVID–19 patients who may require more intensive monitoring, and can be useful for resource allocation.