Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.

Effect of Mineral and Bone Metabolism on Restless Legs Syndrome in Hemodialysis Patients.

STUDY OBJECTIVES: Restless legs syndrome (RLS) is a highly prevalent sleep disease among patients on hemodialysis. The physiopathology is still unclear, and may be multifactorial. Because of the association between iron metabolism and chronic kidney disease-mineral and bone disorders (CKD-MBD), we hypothesized that both factors would be associated with RLS. METHODS: We have evaluated hemodialysis patients, in a face-to-face interview for the diagnosis and severity of RLS, as measured by the International Restless Legs Syndrome Study Group. Clinical, demographic, and biochemical characteristics were measured. RESULTS: Out of 101 adult patients included, RLS was found in 29 (28.7%). Adjusted multinomial regression analysis revealed that age older than 35 years, transferrin saturation less than 47%, serum ferritin level less than 700 ng/mL, hemoglobin level less than 9.8 g/dL, serum phosphate level higher than 5.2 mg/dL, FGF-23 higher than 2,000 RU/mL, and C-reactive protein less than 1.24 mg/dL were independently associated with RLS. RLS was classified as mild, moderate, severe, and very severe in 3.4%, 41.7%, 44.8%, and 10.1% of patients, respectively. Scores of severity correlated significantly with erythropoietin dose/kg/w (p = 0.046), phosphate (p = 0.003), and inversely with serum albumin (p = 0.003) and calcium (p = 0.008). Phosphate and 25(OH)-vitamin D correlated with transferrin saturation. Patients with severe/very severe symptoms were mostly women, presented with lower serum iron, ionic calcium, and serum albumin levels and higher levels of serum phosphate, and higher percentage of 25(OH)-vitamin D deficiency and levels of FGF-23 higher than 2,000 RU/mL than did those with mild/moderate symptoms. CONCLUSIONS: CKD-MBD factors besides iron metabolism are associated with RLS in patients on hemodialysis, providing new insights into the understanding of RLS in this population.

Coronary Artery Calcification Seen Through Chest Radiography.

Patients with end-stage renal disease (ESRD) on dialysis have poor overall survival, and cardiovascular (CV) is the main cause of mortality among these patients. Coronary calcification is an independent predictor of mortality and CV events in dialysis patients and can be accessed by using a computerized tomography scanning. The high cost of this procedure, however, precludes routine implementation of this method for the purposes of risk stratification. Aortic arch calcification has been associated with CV mortality in the general population. Also, vascular calcification beyond the thoracic aorta has been shown to be associated with mortality in ESRD patients. We presented here a case of a young patient with ESRD in which the coronary calcification could be cleared seen through simple chest radiography. This is a 35-year-old man with a history of ESRD secondary to pyelonephritis, who was receiving conventional hemodialysis thrice a week for the last 5 years. He was submitted to chest radiography as part of routine annual cardiac screening. His blood pressure was within the target limits, although much higher in lower limbs, generating a high ankle brachial index of 1.3. He also had secondary hyperparathyroidism. His physical examination was unremarkable, except for the presence of non-functioning arteriovenous fistulas in both arms and a central venous catheter. The last routine blood test showed calcium 9.0 mg/dL, phosphate 5.7 mg/dL, potassium 4.7 mEq/L, creatinine 7.4 mg/dL, alkaline phosphatase 175 U/L, and parathyroid hormone 1,745 pg/mL. Surprisingly, the chest radiography revealed a calcified aortic valve and a calcified coronary artery. This patient had sudden cardiac death few months after this radiography had been taken. We present here a case of coronary calcification that can be seen through simple chest radiography. Such images are not usually seen, although the risk of vascular calcification is high in this population, and is closely related to CV risk. Chest radiographs, nearly universally available provide a method for assessing coronary artery calcification. Such a finding is intriguing and should alert nephrologists and cardiologists for the high risk of CV death in these patients.