PMC:7464116 / 70647-86130 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7464116","sourcedb":"PMC","sourceid":"7464116","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7464116","text":"8. Management of the Nephropathic Patient\nThe patient with chronic kidney disease (CKD) is a fragile patient who in most cases suffers from several comorbidities that predispose to the development of infections [135]. For this reason, after the declaration of the pandemic state by the WHO, protective measures were developed for the patient with CKD without signs of ongoing acute pathology. All nephrology units have been invited to establish a telemedicine system, through which the clinical progress of the patients may be followed. In this way, hospital access was limited only for urgent cases [136].\nFor patients with the need to prepare arterial venous fistula for the initiation of hemodialysis treatment, the centers specializing in vascular access management organized screening of all patients for COVID-19. Interventions for patients with confirmed or suspected infection needed to be carried out in designated premises with the necessary protection for medical staff [137].\nIn addition, for kidney transplants, it was necessary to develop preventive measures that could allow for their management. In particular, each Transplant Center had to evaluate the possibility of performing a kidney transplant in relation to the availability of intensive care units and the risk of ICU admission for the individual patient [138]. In addition, during the course of the COVID-19 pandemic, organ donation and transplantation experienced significant changes: organ authorization decreased by 11%; the number of organs transplanted decreased by 18%; and organ recovery for transplantation fell by 17% [139].\nDialysis patients are even more prone to develop severe infectious diseases than the general population [135]. In fact, in previous epidemics or catastrophic situations, the case fatality rate has always been much higher in dialysis patients than in the general population [137]. In addition, for SARS-CoV-2 infection, patients on hemodialysis treatment have proved to be a population at risk of developing COVID-19. In most cases, in fact, they are patients of advanced age and with many comorbidities (cardiovascular disease, high blood pressure, diabetes and lung disease) often associated with worse prognosis in COVID-19 patients [140,141]. The logistical aspects associated with dialysis treatment further increase the risk of contraction and transmission of the disease. The patient on hemodialysis, in fact, must carry out the treatment generally three times a week and this implies the recurrent access to health structures. Furthermore, the hemodialysis session is performed simultaneously by several patients who inevitably interact with each other [142]. These circumstances, associated with the possibility of non-specific clinical manifestations due to immune suppression related to uremia, cause a higher risk of diffusing the infection in the dialysis ward [83].\nIn some guidance documents, the possibility of performing home hemodialysis with telematic support of the patient and home visits when necessary was also considered [11]. In other papers, however, the reduction of hemodialysis sessions from 3 to 2 times a week has been indicated as an alternative in patients who tolerate this regimen. This would reduce the risk of exposure to infections during transport and the probability of spreading to the dialysis unit or hospital [12].\nBeing prepared for a sudden and high amount of patients, suspected or confirmed, was crucial for the control of COVID-19 infection.\nThe Chinese Society of Nephrology [143], the Centers for Disease Control and Prevention, and also the various dialysis organizations developed guidelines for dialysis units during the COVID-19 epidemic. In addition, the EUDIAL ERA-EDTA working group [137] provided recommendations for the prevention and containment of the emerging SARS-CoV-2 pandemic (COVID-19) in hemodialysis centers.\nThe first step in managing the COVID-19 pandemic in dialysis centers was to ensure training for all healthcare staff. Doctors, nurses and care-workers have been adequately trained on the prevention measures, on the use and disposal of medical devices and any contaminated clothing/objects [137].\nIn all the centers, a member of staff was assigned to perform the nasopharynx swabs for COVID-19 polymerase chain reaction. The indicated professional figures were trained on the correct methods of performing the diagnostic test but also on the type of devices needed during the procedure. Each operator, in fact, must be equipped with a protective mask (FFP2) capable of filtering 95% of particulates and aerosols in the inhaled air, glasses, mobcap, disposable surgical blouse and gloves [137].\nFurthermore, all eligible healthcare staff were trained to perform an accurate telephone triage. The early recognition of suspect patients allows them to be prepared on their arrival, so that they can direct them towards the most suitable path, avoiding interaction with other patients [136].\nThe second crucial step concerned the training of patients in the dialysis center. In fact, it was important that each patient drastically reduced interpersonal interactions outside the dialysis center, limiting exits only to travel to and from dialysis facilities, using individual transport to reach the dialysis center, decreasing contact with family members, especially with children [137]. The pediatric population, in fact, can act as a carrier of the disease often without showing symptoms or showing mild symptoms [144].\nAll patients also received instructions relating to how and when to perform hand hygiene, the use of face masks and the disposal of these and any contaminated objects. Family members living with dialysis patients were also sensitized and prompted to follow precautionary procedures, including measuring body temperature, good personal hygiene, frequent hand washing and prompt reporting of potential infected individuals [137].\nOf course, organizational adjustments had to be made in dialysis centers as well. The preventive measures, in fact, must start from the waiting room. All dialysis centers have had to adapt their waiting rooms to ensure a safe first reception for patients. It is in fact essential that patients come together in large rooms that can allow a distance of at least 2 m between the patients, equipped with air conditioning and ventilation systems capable of removing particles and droplets of aerosol from the air, equipped with distributors of hydroalcoholic solutions for the hygiene of the hands [137,142].\nAdditional preventive measures must be implemented in the transition from the waiting room to the treatment room. All patients must be subjected to temperature measurement and must be encouraged to perform hand hygiene and hygiene of the fistula arm, as well as to practice accurate disinfection of the venipuncture areas [145]. At the end of these steps, the patient equipped with a mask can access the treatment room. These, like the waiting rooms, must be equipped with suitable air conditioning/ventilation systems and must guarantee a distance of at least 2 m between the individual positions [137].\nIf patients with suspected symptoms for COVID-19 (fever, cough, conjunctivitis) are identified after the arrival at the Dialysis Center, these must be immediately isolated and subjected to screening tests. Pending the test results, if hemodialysis treatment is not postponed, the patient should be treated as a confirmed case [145]. Therefore, the patient must dialyze in a default room; the room reserved for HBV positive patients could be adequate if available [142]. If the Center does not have a default room, the patient must wait in an isolated room and receive dialysis treatment at the end of the last shift of the day. If, at the end of the treatment, the result of the swab is not present yet, it is necessary to proceed with the immediate disinfection of the rooms [137]. If the outcome of the swab is negative, patients can return to the dialysis facility [145].\nThe management of patients on dialysis with confirmed COVID-19 infection must be carried out according to strict protocols in order to minimize the risk for both other patients and personnel taking care of these patients.\nMost of the guidelines suggest that dialysis patients, a cause of their management complexity, their fragility and their risk of sudden decompensating, whenever possible, should be hospitalized until complete recovery [145]. The hemodialysis sessions, in this case, can be regularly performed in rooms in isolation or, alternatively, at the patient’s bed with machines usually used for patients with acute renal failure or home hemodialysis machines [136].\nIn the case of an infected patient with mild symptoms and not hospitalized, the hemodialysis sessions must be performed as his therapeutic scheme, in an isolated environment with appropriately organized medical staff [146].\nAll personnel involved in the direct care of COVID-19 patients must undertake full protection, including hair caps, gloves, long-sleeved waterproof isolation clothing, goggles and medical masks (FFP2 or FFP3 mask, if available) filtering 95–99% of particulate matter and aerosols in inhaled air [137,147].\nIt is important not only to avoid contact of these patients with healthy patients, but also to prevent the mixing of suspected and confirmed cases [137].\nIf there are more infected, asymptomatic or paucisymptomatic patients in the same Center, without the need for hospitalization, they can be dialyzed together in a specific section of the unit, preferably as the last shift of the day. A select group of healthcare professionals must be assigned to these patients and must apply all precautionary measures. The hemodialysis room must be properly sanitized at the end of the session and medical waste must be considered highly infectious and disposed of accordingly [137,142].\nIn case of peripheral centers without the possibility of creating conditions for isolation, and where an infectious disease unit and intensive care unit are both not available, patients with suspected or confirmed COVID-19 disease should be moved into hospitals having these facilities [145].\nManagement of the peritoneal dialysis patient was less complex than that of the hemodialysis patient. In fact, they usually carry out purification treatment at their home and go to the nephrological center only for scheduled periodic checks. The pandemic from COVID-19 has made the expansion of a telemedicine network necessary to manage patients from home [124].\nTelematic support was also indispensable for the management of the transplanted patient. Kidney transplant patients need to perform periodic checks at the post-transplant surgery of the nephrological structure of territorial jurisdiction and at the post-transplant surgery of the Center where the transplant was performed. Telemedicine techniques have made it possible to monitor patients remotely and reduce outpatient visits [136].\nFinally, in many hospitals the ordinary nephrological hospitalization wards have been closed due to the need to make space for the “COVID areas”. The setting up of a single room for patients awaiting the result of the screening buffer for COVID-19, was fundamental for the restart of admissions for nephrology patients requiring hospital treatment [136].\nIt is important to emphasize that current guidelines and recommendations relating to the management of renal patients must be considered “provisional” and must undergo continuous reviews and updates in light of new developments.\n\nOverview of Therapy\nCOVID-19 treatment is essentially supportive and, in fact, specific vaccines or therapies are not yet available. The COVID-19 vaccine is considered to be an effective prophylactic strategy. About 90 institutions around the world are working on identifying a specific and safe vaccine [148]. As of 8 April 2020, the global research and development landscape for COVID-19 vaccines has included 115 vaccine candidates. Most of these are currently in the preclinical phase and only some of these (mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio and LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute) have recently moved into clinical development [149].\nThe therapeutic protocols used for the general population have also been adopted in patients with chronic renal failure, regardless of the stage of the disease [150].\nAntiviral drugs (Lopinavir/ritonavir (200/50 mg 2 cp × 2/day), Darunavir (800 mg/day), Ritonavir (100 mg/day), Darunavir/cobicistat (800/150 mg/day)) have been effective for the management of SARS-CoV-2 infection, in asymptomatic/paucisymptomatic patients and in patients with more severe manifestations [150,151].\nHydroxychloroquine (known as an antimalarial drug) was successfully used in the early stages of the pandemic until May 26th, 2020, when AIFA suspended authorization for its use for the treatment of SARS-CoV-2 infection [152,153].\nTocilizumab (anti-IL-6 monoclonal antibody) has been used in association with steroids and/or antiviral drugs, for the treatment of more severe clinical cases and patients with rapidly and significantly increasing levels of D-dimer. The dosage is 8 mg/kg body weight with a maximum infusion dose of 800 mg for a maximum of three administrations [154,155].\nUnlike hydroxychloroquine, both antiviral drugs and tocilizumab do not require dosage adjustments in relation to the values of the glomerular filtrate [150].\nGiven the state of hypercoagulability and the high incidence of thromboembolic complications in COVID-19 patients, high doses of low molecular weight heparin have been added to the therapeutic protocols [156].\nFor kidney transplant patients, immunosuppressive therapy must be reshaped, in particular, mycophenolate, azathioprine and calcineurin inhibitors must be suspended during the active phases of the disease [150]. Tocilizumab, on the other hand, may be effective in these patients, but randomized trials are needed [157].\nFor COVID-19 patients undergoing intermittent dialysis, the methods that obtain the greatest clearance of the pro-inflammatory molecules are preferred; in patients with AKI, hemodynamically unstable and requiring dialysis, continuous dialysis treatments are preferred (CVVH with pre and post-dilution at a dose \u003e 25 mL/Kg/h), using citrate as the first choice anticoagulant (after serial assessments of serum calcium and lactic acid) and, alternatively, unfractionated heparin (constantly monitoring the patient’s APPT) [150].\nInterferons have also been proposed as a possible therapy, although the timing of their use is critical since their benefit is realized if given before or early on in infection and may actually be harmful if given in the later stages. Clinical studies are underway to test their efficacy [158].\nA recent phosphoproteomics analysis of SARS-CoV-2 infected Vero E6 cells (a cell line derived from monkey kidney epithelial cells) showed dramatic changes in phosphorylation of both host and viral proteins. Furthermore, viral infection induced the formation of casein kinase II (CK2)-containing filopodia containing budding viral particles. The authors have stated that pharmacologic inhibition of several kinases including CK2 and p38 MAP (mitogen-activated protein) kinases may be potential future COVID-19 therapies [159].\nA summary of the main contents of this paper is depicted in Table 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