The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UK.

Background: Patients on dialysis with frequent comorbidities, advanced age, and frailty, who visit treatment facilities frequently, are perhaps more prone to SARS-CoV-2 infection and related death-the risk factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in patients on dialysis infected with SARS-CoV-2. Methods: Data on 224 patients on hemodialysis between February 29, 2020 and May 15, 2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using a competing risk-regression model assessed by subdistribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case-fatality ratio of 23% (95% CI, 17% to 28%) overall, but that varies across age groups from 11% (95% CI, 0.9% to 9.2%) in patients ≤50 years old and 32% (95% CI, 17% to 48%) in patients >80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days, indicating a rapid deterioration toward death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in patients who were more frail (WHO performance status, 3-4; SHR, 2.16 [95% CI, 1.25 to 3.74]; P=0.006), had ischemic heart disease (SHR, 2.28 [95% CI, 1.32 to 3.94]; P=0.003), cerebrovascular disease (SHR, 2.11 [95% CI, 1.20 to 3.72]; P=0.01), smoking history (SHR, 2.69 [95% CI, 1.33 to 5.45]; P=0.006), patients who were hospitalized (SHR, 10.26 [95% CI, 3.10 to 33.94]; P<0.001), and patients with high CRP (SHR, 1.35 [95% CI, 1.10 to 1.67]) and a high neutrophil:lymphocyte ratio (SHR, 1.03 [95% CI, 1.01 to 1.04], P<0.001). Our data did not support differences in the risk of death associated with sex, ethnicity, dialysis vintage, or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, in which 13% were affected, revealed that patients who were non-White (62% versus 52% in all patients, P=0.001) and those with diabetes (54% versus 22%, P<0.001) were disproportionately affected. Conclusions: This report discusses the outcomes of a large cohort of patients on dialysis. We found SARS-CoV-2 infection affected more patients with diabetes and those who were non-White, with a high case-fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP, and neutrophil:lymphocyte ratio at presentation.

Endogenous retinoic acid activity in principal cells and intercalated cells of mouse collecting duct system.

BACKGROUND: Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in post-natal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys. METHODOLOGY/PRINCIPAL FINDINGS: RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, ß-galactosidase. Double immunostaining was performed for ß-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules. CONCLUSIONS/SIGNIFICANCE: Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the collecting duct system.

Kidneys of Alb/TGF-beta1 transgenic mice are deficient in retinoic acid and exogenous retinoic acid shows dose-dependent toxicity.

BACKGROUND: Alb/TGF-beta(1) transgenic mice overexpress active transforming growth factor-beta(1) (TGF-beta(1)) in the liver, leading to increased circulating levels of the cytokine and progressive renal fibrosis. This study was designed to explore if exogenous all-trans retinoic acid (tRA) prevents renal fibrosis in this animal model. METHODS: The retinoid profile in kidney and liver of wild-type and Alb/TGF-beta(1) transgenic mice was examined by high-performance liquid chromatography and slow-release pellets containing different amounts of tRA were implanted subcutaneously to treat the Alb/TGF-beta(1) transgenic mice, starting at 1 week of age; mice were sacrificed 2 weeks later. RESULTS: Kidneys of 3-week-old wild-type mice had abundant tRA, which was completely absent in kidneys of the transgenic mice. Low doses of tRA (6-10.7 mg/kg/day) failed to affect renal fibrosis although it tended to suppress the mRNA expression of some molecular markers of fibrosis and retinal dehydrogenase 2 (RALDH2), a gene encoding a key tRA-synthesising enzyme. These tendencies disappeared, mortality tended to increase and RALDH2 and connective tissue growth factor (CTGF) mRNAs significantly increased in the medium-dose group (12.7-18.8 mg/kg/day). High doses (20.1-27.4 mg/kg/day) showed even higher toxicity with increased renal fibrosis and significant mortality. CONCLUSIONS: Alb/TGF-beta(1) transgenic mice are characterised by depletion of endogenous renal tRA. Exogenous tRA dose-dependently increases mortality and kidney fibrosis, which is associated with dose-dependent regulation of renal RALDH2 and CTGF mRNA expression.

Life-threatening rectal bleeding due to cytomegalovirus colitis in a haemodialysis patient.

Cytomegalovirus (CMV) disease is a well-recognized complication in immunocompromised patients such as renal transplant recipients, occurring due to reactivation of latent infection or primary infection. It is, however, uncommon in immunocompetent patients. We report a haemodialysis patient who presented with pyrexia and life-threatening rectal bleeding due to CMV colitis, who had none of the classical risk factors for CMV disease, although was at risk. We review the literature surrounding CMV colitis in immunocompetent patients. This case highlights the importance of considering unusual causes for the common presentation of rectal bleeding in vulnerable patient populations.