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      Rationale for Medium Cutoff Membranes in COVID-19 Patients Requiring Renal Replacement Therapy

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          Abstract

          The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection. Social distancing is the most effective preventive measure to reduce the risk of infection. Nonetheless, the necessity to frequently reach the dialysis center and the inherent social gathering both impede social distancing and also self-quarantine for infected individuals. A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Concomitantly, a condition of relative immunosuppression is also attributed to similar factors. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes, the removal of large middle molecules is scant. Medium cutoff (MCO) dialyzers are a new class of membranes that allow substantial removal of large middle molecules with negligible albumin losses. Recent trials confirmed long-term safety and long-term sustained reduction in the concentration of large uremic toxins with MCO dialyzers. Herein, we discuss the rationale for applying MCO membranes in COVID-19 patients and its possible immunoadjuvant effects that could mitigate the burden of COVID-19 infection in dialysis patients. We also discuss the direct cytopathic effect of the virus on renal tissue and extracorporeal blood purification techniques that can prevent kidney damage or reduce acute kidney injury progression.

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          Most cited references 38

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          Is Open Access

          Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients—A Randomized Controlled Clinical Trial

          Background To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients. Methods The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines. Results After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p<0.001)-α and IL-6 mRNA (RQ from 0.78 ± 0.80 to 0.60 ± 0.43, -23.1%, p<0.01) was reduced to a significantly greater extent than with High-flux dialyzers (TNF mRNA-RQ: -14.3%; IL-6 mRNA-RQ: -3.5%). After retransformation of logarithmically transformed data, measurements after MCO were reduced to 82% of those after HF (95% CI 74%–91%). 4 weeks use of MCO-Ci resulted in long-lasting change in plasma levels of several cytokines and other substances with a significant decrease for sTNFR1, kappa and lambda free light chains, urea and an increase for Lp-PLA2 (PLA2G7) compared to High-flux. Albumin levels dropped significantly after 4 weeks of MCO dialysis but increased after additional 8 weeks of MCO dialysis. Twelve weeks treatment with MCO-Ci was well tolerated regarding the number of (S)AEs. In the extension period levels of CRP, TNF-α-mRNA and IL-6 mRNA remained stable in High-flux as well as in MCO-Ci. Conclusions MCO-Ci dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers. Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis. Serum albumin concentrations stabilize after an initial drop. These results encourage further trials with longer treatment periods and clinical endpoints.
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            The immunology of COVID-19: is immune modulation an option for treatment?

            Summary In December, 2019, an outbreak of COVID-19 emerged in Wuhan, China and quickly spread globally. As of May 7, 2020, there were 3 672 238 confirmed infections and 254 045 deaths attributed to COVID-19. Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0–24 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.
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              Presenting Characteristics, Comorbidities, and Outcomes among 5700 Patients Hospitalized with COVID-19 in the New York City Area

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                Author and article information

                Journal
                Nephron Clin Pract
                Nephron Clin Pract
                NEF
                Nephron. Clinical Practice
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1660-8151
                1660-2110
                4 August 2020
                : 1-5
                Affiliations
                [1 ] aDepartment of Medicine (DIMED), University of Padova, Padova, Italy
                [2 ] bDepartment of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza, San Bortolo Hospital, Vicenza, Italy
                [3 ] cDepartment of Nephrology, Clínica de Doenčas Renais de Brasília, Brasília, Brazil
                [4 ] dDepartment of Health Sciences, University of Milan, Milan, Italy
                [5 ] eDepartment of Nephrology and Dialysis, ASST Santi Paolo e Carlo, Milan, Italy
                Author notes
                *Claudio Ronco, Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Viale Rodolfi, 37, IT–36100 Vicenza (Italy), cronco@ 123456goldnet.it
                Article
                nef-0001
                10.1159/000509807
                7490487
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                Page count
                References: 36, Pages: 5
                Categories
                Clinical Practice: Review Article

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