Prevalence and predictors of outcomes among ESRD patients with COVID-19.

BACKGROUND: End-stage renal disease patients on hemodialysis (ESRD) patients are at high risk for contracting COVID-19. In this propensity matched cohort study, we examined the prevalence of COVID-19 in emergency room (ER) patients and examined whether clinical outcomes varied by ESRD status. METHODS: Patients who visited George Washington University Hospital ER from April 2020 to April 2021 were reviewed for COVID-19 and ESRD status. Among COVID-positive ER patients, the propensity for ESRD was calculated using a logistic regression model to create a propensity-matched sample of ESRD vs non-ESRD COVID-19 patients. A multivariable model examined whether ESRD was an independent predictor of death and other outcomes in COVID-19 patients. RESULTS: Among the 27,106 ER patients, 2689 of whom were COVID-positive (9.9%). The odds of testing positive for COVID-19 were 0.97 ([95% CI: 0.78-1.20], p = 0.76) in ESRD vs non-ESRD patients after adjusting for age, sex, and race. There were 2414 COVID-positive individuals with non-missing data, of which 98 were ESRD patients. In this COVID-positive sample, ESRD patients experienced a higher incidence of stroke, sepsis, and pneumonia than non-ESRD individuals. Significant independent predictors of death included age, race, sex, insurance status, and diabetes mellitus. Those with no insurance had odds of death that was 212% higher than those with private insurance (3.124 [1.695-5.759], p < 0.001). ESRD status was not an independent predictor of death (1.215 [0.623-2.370], p = 0.57). After propensity-matching in the COVID-positive patients, there were 95 ESRD patients matched with 283 non-ESRD individuals. In this sample, insurance status continued to be an independent predictor of mortality, while ESRD status was not. ESRD patients were more likely to have lactic acidosis (36% vs 15%) and length of hospital stay ≥ 7 days (48% vs 31%), but no increase in odds for any studied adverse outcomes. CONCLUSIONS: In ER patients, ESRD status was not associated with higher odds for testing positive for COVID-19. Among ER patients who were COVID positive, ESRD was not associated with mortality. However, insurance status had a strong and independent association with death among ER patients with COVID-19.

G Protein-Coupled Receptor 37L1 Modulates Epigenetic Changes in Human Renal Proximal Tubule Cells.

Renal luminal sodium transport is essential for physiological blood pressure control, and abnormalities in this process are strongly implicated in the pathogenesis of essential hypertension. Renal G protein-coupled receptors (GPCRs) are critical for the regulation of the reabsorption of essential nutrients, ions, and water from the glomerular filtrate. Recently, we showed that GPCR 37L1 (GPR37L1) is expressed on the apical membrane of renal proximal tubules (RPT) and regulates luminal sodium transport and blood pressure by modulating the function of the sodium proton exchanger 3 (NHE3). However, little is known about GPR37L1 intracellular signaling. Here, we show that GPR37L1 is localized to the nuclear membrane, in addition to the plasma membrane in human RPT cells. Furthermore, GPR37L1 signals via the PI3K/AKT/mTOR pathway to decrease the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and enhance NHE3 transcription. Overall, we demonstrate the direct role of a nuclear membrane GPCR in the regulation of renal sodium through epigenetic gene regulation.

Alterations of gut microbial pathways and virulence factors in hemodialysis patients.

Alterations in gut microbiota might contribute to uremic toxicity and immune dysregulation in patients with end-stage renal disease. Hemodialysis patients are prone to infection and higher mortality following sepsis. The virulence factors in the gut metagenome have not been well studied in hemodialysis patients, which could be employed by microorganisms to successfully thrive and flourish in their hosts. In this study, we performed shotgun metagenomics sequencing on fecal DNA collected from 16 control subjects and 24 hemodialysis patients. Our analysis shows that a number of microbial species, metabolic pathways, antibiotic resistance, and virulence factors were significantly altered in hemodialysis patients compared with controls. In particular, erythromycin resistance methylase, pyridoxamine 5-phosphate oxidase, and streptothricin-acetyl-transferase were significantly increased in hemodialysis patients. The findings in our study laid a valuable foundation to further elucidate the causative role of virulence factors in predisposing HD patients to infection and to develop treatment strategies to reduce the genetic capacities of antibiotic resistance and virulence factors in HD patients.