COVID-19 is spreading globally with the angiotensin converting enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This raised concerns how ACE2 and the Renin-Angiotensin (Ang)-System (RAS) are to be dealt with given their roles in hypertension and their involvement in COVID-19's morbidity and mortality. Specifically, increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by increasing SARS-CoV-2 binding sites. However, ACE2 is part of the protective counter-regulatory ACE2-Ang1-7-MasR axis, which opposes the classical ACE-AngII-AT1R regulatory axis. We used Gitelman's and Bartter's syndromes (GS/BS) patients, rare genetic tubulopathies that have endogenously increased levels of ACE2, to explore these issues. Specifically, 128 genetically confirmed GS/BS patients, living in Lombardia, Emilia Romagna and Veneto, the Northern Italy hot spots for COVID-19, were surveyed via telephone survey regarding COVID-19. The survey found no COVID-19 infection and absence of COVID-19 symptoms in any patient. Comparison analysis with the prevalence of COVID-19 in those regions showed statistical significance (p < 0.01). The results of the study strongly suggest that increased ACE2 does not increase risk of COVID-19 and that ACEi and ARBs by blocking excessive AT1R-mediated Ang II activation might favor the increase of ACE2-derived Ang 1-7. GS/BS patients' increased ACE2 and Ang 1-7 levels and their characteristic chronic metabolic alkalosis suggest a mechanism similar to that of chloroquine/hydroxychloroquine effect on ACE2 glycosylation alteration with resulting SARS-COV-2 binding inhibition and blockage/inhibition of viral entry. Studies from our laboratory are ongoing to explore GS/BS ACE2 glycosylation and other potential beneficial effects of BS/GS. Importantly, the absence of frank COVID-19 or of COVID-19 symptoms in the BS/GS patients cohort, given no direct ascertainment of COVID-19 status, suggest that elevated ACE2 levels as found in GS/BS patients at a minimum render COVID-19 infection asymptomatic and thus that COVID-19 symptoms are driven by ACE2 levels.
COVID-19 often leads to acute respiratory distress syndrome complicated by acute kidney injury (AKI). The indications for renal replacement therapy for these patients are those commonly accepted to treat AKI. We describe a continuous veno-venous haemodialysis (CVVHD) protocol for AKI, which aims to provide the best treatment according to the particular patient’s and medical personnels’ needs in biohazard settings with limited human and technological resources. We designed a CVVHD protocol with a high cut-off (HCO) filter in regional citrate anticoagulation (RCA). The HCO filter in diffusion determines the enhanced cytokines clearance with less filter clotting due to a lower filtration fraction. In our hospital, at the beginning of the pandemic outbreak, we treated seven COVID-19 patients with AKI stage 2 and 3 and recorded the circuit lifespan and the number of interventions on monitors. CVVHD in RCA appears to be safe, effective and easy to be performed in a biohazard scenario using lower blood flows and less bag changes with fluid savings, a biohazard reduction and sparing of resources. Although the data come from a very small cohort, our protocol seems related to a low mortality.
Acute decompensated heart failure (ADHF) has the highest rate of hospital re-admission among all medical conditions and portends a significant financial burden on healthcare systems worldwide. Hospitalization for ADHF is primarily driven by congestion, with intravenous loop diuretics representing the cornerstone of therapy. However, it is well described that a significant subset of patients are discharged with residual fluid overload. While the cause of the incomplete decongestion is multifactorial, development of diuretic resistance is a well-characterized contributing factor with consequent poor outcomes. Moreover, the therapeutic response to diuretics is known to lack predictability. Extracorporeal ultrafiltration (a mechanical pump-driven therapy) has emerged as an option to overcome shortcomings of the diuretics. It allows clinicians to customize the volume and rate of fluid removal to the needs and clinical characteristics of the patients. The results of the currently available studies indicate that this therapy is associated with more efficient fluid and sodium removal comparted to medical therapy, hence leading to reduction in the rate of re-admissions and a potential salutary impact on the financial burden associated with the care of these patients. While isolated ultrafiltration can be performed by conventional machines used for renal replacement therapy, the advent of simplified, portable, and user-friendly devices that are specifically designed for extracorporeal ultrafiltration therapy has further enhanced the interest in this therapeutic modality and increased the potential for its more widespread use. Further development in this direction through device miniaturization may extend the horizons of indications and the applicability of this therapy even in the ambulatory settings.
Introduction. Fluid overload has been associated with untoward outcomes in a variety of clinical settings. Isolated extracorporeal ultrafiltration (UF) allows for mechanical extraction of excess fluid and optimization of volume status without the established risks associated with use of high dose diuretics. Conventional machines for renal replacement therapy can be used to perform isolated UF. However, they typically need high blood flow rates with high circuit volumes and the therapy has to be performed by trained nurses. Herein, we describe a novel device, the Artificial Diuresis-1, or AD 1 (Medica S.p.A., Medolla, Italy), which is a portable technology designed to perform extracorporeal UF at bedside. Materials and Methods. The AD 1 uses a polysulfone mini-filter to generate ultrafiltrate with the help of two forces: blood flow (Qb) and gravity (based on the height at which the ultrafiltrate collection bag is placed). In vitro experiments were performed using human blood to evaluate vascular access pressures and ultrafiltrate volumes using various central venous catheters (12 Fr bilume, 10 Fr with 2 separate lumens, pediatric catheter 7 Fr). A variety of combinations were tested with Qb of 20, 35, 50 mL/min and collection bag height at 20, 40, 60 cm, measuring the UF rate per minute each while monitoring the pressures in the venous and arterial lines and filtration fraction. Results. The device’s performance was as expected. Regarding the pediatric CVC, it was possible to perform measurements only with a Qb of 20 mL/min due to increased venous pressure. Ultrafiltration rates when lines were directly connected to the blood container as well as for CVC Tesio ranged from 3.7 to 11 mL/min, for the CVC Niagara™ from 4.5 to 12.5 mL/min and for the CVC 7 Fr from 8.5 to 10 mL/min. The pressures of the vascular accesses were kept within a range of -5/-40 mmHg for the artery and +10/+70 mmHg for the vein. The highest venous pressure values were found with the CVC 7 Fr (+80/+100 mmHg). Conclusions. This novel device allows to treat patients with fluid overload in a variety of settings, from low-intensity department such as long-term care facilities to the intensive care unit. The device is small and portable, has a simple design, and is user-friendly. Future studies will be needed to evaluate whether gentle ultrafiltration and treatment of volume overload will translate into improvement in clinical outcomes such as a reduction in congestion-related hospital admission.
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