ΕΛΛΗΝΙΚΟ ΚΟΛΛΕΓΙΟ ΝΕΦΡΟΛΟΓΙΑΣ ΚΑΙ ΥΠΕΡΤΑΣΗΣ

This text has been prepared by the ERA-EDTA Immunosuppression Working Group (IWG)

To health care authorities
Kidney patients using immunosuppression should be regarded as a high-risk group. Many of them are elderly and many have impaired kidney function and other co-morbidities known that enhance risk of adverse outcome of the COVID-19 infection. They use drugs that suppress the natural immune system and many of them have impaired kidney that in itself decreases immune functions. Taken together it is likely that this group will have a higher risk to have a more severe disease course when infected with the new Coronavirus. Authorities on all levels need to facilitate for these patients to be home on sick leave as a preventive measure to reduce individual risks and on a population level the burden of hospitalizations. Patients with co-morbidities such as CKD requiring immunosuppression will most probably consume more health-care resources when infected.

To clinicians
Background: Cases with the Corona virus SARS CoV 2 infection that cause COVID-19 have been detected in all European countries. In many areas there is transmission in the community. Personal communications from China suggest that CKD-patients treated with immunosuppression (IS) have the same risk of infection as the background population. Most COVID-19 infections are mild and self-limited, however, a published report from the US suggest that patients on IS (mainly transplant recipients) have an increased risk of severe disease. However, one publication on liver transplant recipients, emanating from a pediatric hospital in Italy, did not report of an adverse outcome in their cohort. Preliminary data from the “Brescia Renal COVID Task Force” on 20 renal transplant patients admitted with pneumonitis are circulating: despite a short median follow-up (7 days) 5/20 patients died; of note immunosuppression of this cohort has been managed with withdrawn of MMF/AZA, CNIs and mTOR inhibitor to be replaced by methylprednisolone 16 mg according to a protocol recently presented to the European renal community (https://www.era-edta.org/en/wp-content/uploads/2020/03/COVID_guidelines_finale_eng-GB.pdf).
Very little is known about the effect of IS in glomerulonephritis (GN) / vasculitis (AAV) patients with COVID-19 infection. In Brescia, up to the 22 of March, no patients on immunosuppressive treatment due to primary or secondary glomerulonephritis have been admitted or known to have symptoms imputable to SARS-Cov-2 infection; these patients were advised to respect social distancing rules since early stages of the coronavirus crisis.

Regarding patients in areas with few cases and no known community transmission of the virus

• Inform patients to avoid travelling.
• Recommend patients to keep stocks of drugs at home.
• Make new individual risk-benefit assessments and consider for instance postponing cytotoxic drugs and rituximab (RTX) treatment given as maintenance therapy for AAV or GN, keeping in mind that relapses are detrimental.
• Reschedule visits for patients with mild renal disease to give room for consultations with patients on immunosuppressive drugs before there is community spread in your area.
• Prioritize among patients with indication for renal biopsy, and postpone biopsies that can wait.

Regarding patients in areas with many cases and/or community transmission of the virus, but without known exposure to the virus

• Stay updated and follow the scientific development in the field and be aware that clinical advice may change rapidly as experience grow.
• Recommend patients to practice physical distancing and follow region / country public regulations on quarantine. See recommendations for CKD patients in general.
• Reduce patient traveling by replacing office visits with video or telephone consultations. Recommend your patients to have drugs delivered to their home by relatives or courier service.
• Reschedule visits for patients with mild renal disease to give room to contact patients on immunosuppressive drugs over-phone that you would like to inform about the virus and to assure that they adhere to their treatment whether changed or not.
• Patients in high risk situations (medical staff, employees that encounter significant exposure to people) should be given a letter from their health care provider explaining why they require reassignment of duties or working from home.
• Kidney biopsies in general should only be performed in urgent cases.
• Patients with newly diagnosed GN or AAV need to have decisions made about IS treatment regimen based on disease progress, biopsy findings, kidney function, level of proteinuria and co-morbidities. In disease with slow progression rate, normal kidney function and asymptomatic proteinuria consider mitigation with ARBs, blood pressure control and salt restriction until worst epidemic phase has passed.
• Make a new individual risk-benefit assessment for all immunosuppressive therapies in CKD patients. The evidence for a positive effect of IS for any specific disease is very important for this assessment. Be restrictive in diseases such as IgAN and secondary FSGS; but keep in mind that relapse of vasculitis or nephrotic syndrome may impose a greater risk compared to the effect of maintenance therapy if infected. In general, most otherwise healthy patients should not discontinue immunosuppressive treatment. Patients who have been in sustained remission for some time, could begin decreasing IS. Current tapering of IS should continue at least as planned.
• The individual risk-benefit assessment should take into account the possibility for the patient to practice physical distancing.
• Nephrotic syndrome leads to an immunocompromised state, postponing treatment might increase risk more than IS; especially in cases with deteriorating filtration rates or significant dysfunction at diagnosis.
• Consider postponing RTX for maintenance therapy; although there is no evidence this makes a difference; this is an opinion-based suggestion based on the fact that a dose of RTX reduces the ability to mount a new antibody response for several months. In addition, postponing RTX infusions reduces patient travel, a protective measure in itself.
• Hydroxy chloroquine phosphate (HCQ), has been suggested as possible treatment for the SARS CoV-2. There is no reason to stop such therapy when ongoing (used in SLE or RA). Be aware of HCQ interaction with other drugs, dose adjustments of CNI (mainly ciclosporin), mTOR inhibitors and Tamoxifen are needed.
• Advise GFR correlated dosing. Awareness of possible adverse effects needed.
• HCQ is not yet approved for prophylaxis by CDC or WHO even though some local hospital protocol suggests it. Risk of depleting stocks and depriving patients on current medication with HCQ need to be taken into account.
• Steroid treatment in COVID-19 appears problematic. Steroids have been used widely in ICU-settings at severe virus infections /ARDS, but previous studies on SARS and influenza have shown no benefit and seem to prolong time to viral clearance at all stages of disease. There is possibly an indication of steroids to counteract the cytokine storm in severe cases.

Regarding CKD patients on IS exposed to SARS CoV 2 (no symptoms, infection not confirmed)

• Practice isolation at home.
• Test for the virus, patients on IS may shed virus longer and when asymptomatic.
• Reduce steroids to equivalent of a prednisolone dose of 0.2mg/kg/d if possible.
• If leukopenia / lymphopenia is detected reduce dose of cytotoxic drugs until WBC recovers. Lymphopenia could be a sign of active COVID-19.
• If patients have hypogammaglobulinemia, intravenous IgG (IVIg) can be considered since this might also protect from secondary infections.
• If apheresis is indicated use FFP not albumin for replacement.
• Based on current evidence do not stop ARBs or ACEIs.

Regarding CKD patients on IS with proven COVID 19 infection but no or only mild symptoms

• Communicate importance of physical distancing and hygiene advise.
• Consider stopping or reducing antimetabolites (MMF, AZA). Corticosteroids should never be stopped abruptly. Reduce prednisolone to 0.2mg/kg/d. CNI, or at least ciclosporin might reduce virus replication. Discuss with infection medicine specialist.
• Postpone planned CYC and RTX drug administrations.
• Hospitalization based on symptoms and risk factors. Most patients can remain at home as long as symptoms are mild to moderate. Consider to follow-up the development by phone every 24-48 hours. Inform patient to be observant of progressive symptoms with difficulties breathing or high temperatures not responding to antipyretic treatmen.
• Assess levels of immunosuppression (WBC, immunoglobulins, CD19 and T-cell counts).
• If patients have hypogammaglobulinemia, intravenous IgG (IVIg) can be considered since this might also protect from secondary infections. Keep the risk of transmission to others in mind.
• Based on current evidence do not stop ARBs or ACEIs.

Regarding CKD patients on IS with COVID-19 and overt symptoms.

• Contact infection medicine specialist and specialist on vasculitis/GN GN for discussion of IS adjustment and therapy regimen.
• Several new drugs are being tested. Anti-viral therapy can be given off-label depending on availability and local practices. Please assist your infection medicine specialist on pharmacokinetic considerations in patients with reduced GFR.

This text has been prepared by the ERA-EDTA Working Group EUDIAL for patients on dialysis

The information in this section of the ERA-EDTA Covid-19 webpage is for a large part derived from the website of the Center of Disease Control (CDC). The site’s specific webpage for nephrologists and other professionals working with people on dialysis is very helpful, and contains much practical information. We urge you therefore to consult this webpage:
https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/dialysis.html
Please note that information may change over time. Please check this CDC webpage therefore regularly

General considerations

• A working team consisting of dialysis physicians, nursing staff and technicians should receive training in updated clinical knowledge of epidemic COVID-19, epidemic prevention tools, and guidelines from the government, scientific societies and hospital authorities. Instructions should include how to use facemasks, how to use tissues to cover nose and mouth when coughing or sneezing, how to dispose of, preferably disposable paper, tissues and contaminated items in waste receptacles, and how and when to perform hand hygiene. Training can be done peer to peer or online.
• Latest care recommendations and epidemic information should be updated and delivered to all medical care personnel as needed.
• Staff members should self-monitor their symptoms (if any) and should inform the team leader in case they or their family members develop symptom(s) suggestive of COVID-19 infection. Sick members of the team should stay at home, and in any case should not be in contact with patients or other team members.
• Nurses should be trained to perform nasopharynx swab for COVID-19 PCR, with appropriate dressing (FFP2 mask, goggles, mobcap, disposable surgical blouse, gloves).
• Body temperature should be systematically measured before the start and at the end of the dialysis session in all patients.
• Early recognition and isolation of individuals with respiratory infection is mandatory: 1. dialysis facilities should identify patients with signs and symptoms of fever, cough, upper airway involvement or conjunctivitis before they enter the waiting room and treatment area; 2. instruct patients to call ahead to report fever or respiratory symptoms; thus, the facility can be prepared for their arrival (preferably they should be seen at a first aid department and not on a dialysis department) or triage them to a more appropriate setting (e.g., an acute care hospital); 3. patients must inform staff of fever or respiratory symptoms before arrival at the facility by phone or appropriate electronic means; 4. patients with respiratory symptoms should be brought to an appropriate treatment area as soon as possible in order to minimize time in waiting areas; 5. all patients who have fever, cough, upper airway involvement or conjunctivitis should be screened for novel Coronavirus infection. For sampling, patients should be either in a single-patient room, or in a room dedicated to sampling. Disinfection of the room after sampling is mandatory.
• Ideally, symptomatic patients should be dialyzed in a separate isolated room (if available), in which a negative pressure can be processed, with the door closed. Otherwise, they should wait in a separate isolated room and given dialysis in the last shift of the day until infection is excluded. He/she should wear a proper (surgical or N95) mask filtering 95% of the particulate matter smaller than 2.5 µm in the aerosol of exhaled air.
• Patients with confirmed COVID-19 infection should be admitted to an airborne infection isolation room and should not receive dialysis in an outpatient dialysis facility, unless an airborne infection isolation room is available. All personnel involved in the direct care of patients affected by COVID-19 must undertake full protection, including long-sleeved waterproof isolation clothing, hair caps, goggles, gloves and medical masks (FFP2 or FFP3 mask if available) filtering 95 to 99% of particulate matter and aerosols in inhaled air. Hand hygiene must be strictly implemented: carefully washing hands with soap and water and systematically using alcoholic solutions and disposable gloves.
• Consideration should be given to cohorting more than one patient with suspected or confirmed COVID-19 and the healthcare team caring for them together in the section of the unit and/or on the same shift (e.g., consider the last shift of the day). Avoid, however, mixing of suspected and confirmed cases.
• Healthcare team should be cohorted, i.e., separate teams for management of high-risk and low risk patients. Only the minimum number of assigned healthcare team should enter the isolation room/cohort area, all non-scheduled team-mates should be excluded at all times.
• If a newly confirmed or highly suspected case of novel Coronavirus infection in dialysis centres is identified, disinfection must be carried out immediately. Areas in close contact with these patients must not be used for other patients until cleared.
• The medical waste from confirmed or suspected patients with novel Coronavirus infection must be considered as infectious medical waste and disposed accordingly.

Duration of isolation precautions for patients under investigation for or with confirmed COVID-19

• Until information is available regarding viral shedding after clinical improvement, discontinuation of isolation precautions should be determined on a case-by-case basis, in conjunction with local, regionalstate, and national health authorities.
• Factors that should be considered include: presence of symptoms related to COVID-19 infection, date symptoms resolved, other conditions that would require specific precautions (e.g., tuberculosis, Clostridioides difficile), other laboratory information reflecting clinical status, alternatives to inpatient isolation, such as the possibility of safe recovery at home.

Operations

Patients who need vascular access surgery should be screened for COVID-19. Operations on patients with confirmed or suspected COVID-19 infection should be carried out in a designated room with necessary protection for medical staff.

Home haemodialysis and peritoneal dialysis

These patients should be assisted at home as far as is possible, using telereporting assistance or other electronic systems for clinical management and to supplement home visits by healthcare staff, as deemed necessary.

Considerations

It can be considered to decrease the frequency of hemodialysis sessions from three to two times per week in patients that tolerate such a regimen. This could be considered

• to decrease the need for travelling by taxi / ambulance in case of shortage of such transportation means
• to decrease the chance of dialysis patients getting infected by travelling back and forth to the dialysis unit
• to decrease the chance of dialysis patients spreading the infection to the dialysis unit or the hospital
• to decrease the need for supplies of which shortages are expected. Especially with factories closing down (temporarily) and supply problems, your unit may run into logistical problems with shortage of material needed for dialysis. An early change from three to two hemodialysis sessions per week in a large part of your dialysis population may help to save material, allowing you to run your dialysis unit as long as possible.

ERA-EDTA sharing Milano experience on coronavirus management in dialysis centers

While considering that patients on dialysis treatment are undoubtedly more exposed to contracting infectious diseases and to have more severe manifestations than the non-dialysis population, nephrologists from the Milano dialysis unit argue that there is NO reason to adopt specific prophylactic measures for the entire dialysis population. In their opinion common sense and individual protection rules as for other high risk subjects should prevail.

Author: Professor Mario Cozzolino, MD, PhD, Renal Unit, San Paolo Hospital and San Carlo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy

Read the complete text here: Milano experience on coronavirus management in dialysis centers by Prof. Mario Cozzolino, Milan, Italy

2020-04-06: ERA-EDTA WG Descartes expert opinion regarding the management of immunosuppressive medication for
kidney transplant patients during the COVID-19 pandemic.

https://www.era-edta.org/en/wp-content/uploads/2020/04/Expert-opinion-on-ISD-in-Covid-19.pdf

This text has been prepared by the ERA-EDTA Working Group Descartes for patients living with a kidney transplant

There are several guidelines that are adapted frequently and may differ according to epidemiological characteristics of the specific country as well as availability of resources. Health care professionals are therefore advised to follow local / regional / national guidelines. In addition, the most recent information can be found on the websites of WHO and the Center for Disease Control and Prevention (see below, but see especially the section ‘Relevant websites’).

It can be considered to cancel living and/or deceased donor kidney transplantations. Although there are no general guidelines, the following arguments may help in making such difficult decisions:

• Kidney transplantation is not a live-saving procedure in the short term
• Withholding a dialysis patient a suitable transplant kidney will increase the time on dialysis with associated morbidity and mortality
• Patients requiring induction therapy with anti-T or anti-B cell antibodies may be at increased risk for a severe course of COVID-19
• A shortage of health care professionals and available resources (ICU beds, drugs, material for viral testing) will impede the quality of care after transplantation

Weblinks of interest:

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management

https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html

The American Society of Transplantation (AST) Infectious Disease Community of Practice (IDCOP) developed a frequently asked questions sheet to relay information on the current state of COVID-19 knowledge after receiving queries from transplant colleagues across the world. Please review this FAQ document for information: https://www.myast.org/sites/default/files/COVID19%20FAQ%20Tx%20Centers%202020.03