COMDORA-SBN recommendations for patients with rare kidney diseases in relation to the Covid-19 pandemic



## Resumo
Durante a pandemia da Covid-19, fica a questao de como manter o atendimento adequado aos portadores de outras doencas. O Comite de Doencas Raras (COMDORA) da SBN neste documento da algumas orientacoes ao atendimento de pacientes com doencas renais raras. Estes pacientes devem seguir as recomendacoes destinadas a populacao geral tendo em mente que, por serem portadores de doenca renal cronica, estao incluidos no grupo de risco para desfechos mais graves, caso venham a desenvolver a Covid-19. Procedimentos nao essenciais para tomada de decisao devem ser adiados. Deve-se optar por contatos a distancia, como teleconsultas, e coletas de exames domiciliares (se possivel) nos casos estaveis sob tratamento adequado. Na presenca de sintoma ou sinal de descompensacao da doenca de base ou infeccao pelo Sarscov-2, orientar o paciente a procurar a equipe medica. O paciente nao deve ficar esperando o quadro agravar-se. Alteracoes na prescricao so devem ser feitas com embasamento cientifico. Nao se recomenda a suspensao ou alteracao posologica, mesmo nos casos em que o paciente necessita ir a um centro para receber sua medicacao; neste caso o centro de infusao deve seguir as recomendacoes do Ministerio da Saude. Caso o paciente desenvolva a Covid-19 e faca uso de alguma droga, verificar a necessidade de ajuste nas doses dos medicamentos rotineiros. Evitar o uso de antimetabolicos e antiCD20 nos pacientes com a Covid-9, por reduzirem o clareamento viral e predisporem a infeccoes bacterianas. O contato entre paciente e equipe medica e essencial; alteracoes sao recomendadas apenas com orientacao medica especializada.
Palavras-chave: Doenca Renal Cronica; Doencas Raras; Covid-19; Sars-cov-2.

# Abstract
During the Covid-19 pandemic, the issue is how to maintain adequate care for people with other diseases. In this document, the SBN Rare Diseases Committee (COMDORA) gives some guidelines on the care of patients with rare kidney diseases. These patients should follow the recommendations for the general population, bearing in mind that, as they have chronic kidney disease, they are included in the risk group for more serious outcomes if they develop Covid-19. Non-essential decision-making procedures should be postponed. In stable cases under appropriate treatment, we must choose to contact our patients remotely, using teleconsultations and home exam collections (if possible). In the presence of a symptom or sign of decompensation of the underlying disease, or infection with Sars-cov-2, advise the patient to seek medical assistance. The patient should not be waiting to get worse. Changes to the prescription should only be made on a scientific basis. Dosage suspension or change is not recommended, even in cases in which the patient needs to go to a center to receive his medication; in this case, the infusion center must follow the recommendations of the Ministry of Health. If the patient develops Covid-19 and uses any drugs, check the need for dose adjustment of the routine medications. Avoid the use of antimetabolics and anti-CD20 in patients with Covid-19, as they reduce viral clearance and predispose to bacterial infections. Contact between the patient and the medical team is essential; changes are recommended only with specialized medical guidance.
Keywords: Chronic kidney disease, rare diseases, Covid-19, Sars-cov-2.

## General recommendations
- Social isolation.
- Thoroughly sanitize hands with water and soap (liquid or foam), or alcohol gel with a final concentration of 70%.
- Wear a protective mask in public environments in general. Look for guidelines as to the type of fabric used to make the mask, its durability and the possibility of being properly reused or discarded.
- If you need to cough or sneeze the moment you are without the mask, cover your nose and mouth with your flexed elbow or tissue (and discard it immediately after use).
- Use disposable tissue for nasal hygiene (dispose of it immediately after use and perform hand hygiene).
- Avoid touching mucous membranes of the eyes, nose and mouth -if necessary, perform hand hygiene previously.
- Keep the rooms ventilated.
- Keep clean those surfaces that can be touched frequently (cell phones, computers, door handles, etc.).

## How to handle cases of patients with rare kidney diseases during the pandemic
- The most important thing is not to lose contact with the patient and have a channel available for the patient or family to make contact with the medical team. Therefore, keep the patient's contact updated in the medical record.
- Postpone, if possible, in-person medical consultations and collection of non-essential tests. Use telemedicine and, if possible, blood collection at home 1 .
- Instruct the patient to make contact with the medical team to receive the guidelines, or the professional himself can make contact with the patient to pass on the guidelines.
- Carry out face-to-face consultations and tests when there are doubts about the patient's evolution, or if new symptoms or signs arise.
- Instruct the patient to seek medical care if he has any symptoms related to decompensation of the underlying disease or any complication that may be related to the treatment of the underlying disease.
- Instruct the patient to contact the medical team if symptoms suggestive of SARS-CoV-2 infection occur, so that he/she can receive instructions regarding the need to go to a medical service for clinical, laboratory or imaging exam, or any intervention if necessary. THE PATIENT SHOULD NOT WAIT FOR THE SYMPTOMS TO WORSEN AND THEN LOOK FOR MEDICAL ASSISTANCE. The symptoms seen in transplanted patients using immunosuppressants and who developed Covid-19 were similar to those in the general population, as per shown in2,3,4 .
- Assess, on a case-by-case basis, the possibility of initiating immunosuppression in the indicated cases and try to postpone it in patients in whom this is possible (stable renal function, oligosymptomatic patients, without risk of significant complications) 1 .
- At this time of the Covid-19 pandemic, renal biopsy for diagnostic clarification should be performed only in critical cases for decisionmaking purposes. Protocol biopsies should be postponed 1 .
- Patients with glomerular diseases, in which the delay in immunosuppressive treatment may determine worsening of renal function, this should be promptly instituted, as, for example, in patients with SLE classes III and IV, or in the case of rapidly progressive glomerulonephritis, as well as in patients with active nephrotic syndrome, symptomatic and at risk for thromboembolic phenomena 1 .
- Avoid the use of anti-CD20 therapy, such as rituximab, since there are but a handful of reports in the literature, and patients with low levels of immunoglobulin have a higher risk of secondary infection and less viral clearing 1 .
- Patients compensated for glomerulopathy under immunosuppression should not have their medication suspended, due to the risk of recurrence. If possible, maintain the treatment with the same doses of immunosuppressants or reduce slowly, when indicated, monitoring side effects and clinical and laboratory evolution, in order to avoid decompensation and the need for hospitalization 1 . The home use of test tape or test with sulfosalicylic acid or trichloroacetic acid to assess proteinuria is very appropriate, as it can alert you early on the loss of proteins, before the patient clinically decompensates. In this case, the patient should be instructed to contact the medical team promptly.
- The attending physician must individually assess the possibility of early weaning and suspension of immunosuppression in cases of stable patients in complete remission of the underlying disease and without immediate risk of relapse. Do not abruptly suspend corticosteroids, due to the risk of adrenal insufficiency.
- In infected patients, when desired to reduce the dose of prednisone, a reduction of 0.2 mg/kg/ day is indicated 1 .
- In infected patients, watch the lymphocyte count and discontinue cytotoxic and antimetabolic medications 1 .
- There is no evidence for suspending reninangiotensin-aldosterone system (RAAS) inhibitors, such as ACEI or BRA. These drugs must be maintained 5 , as withdrawal can lead to renal and/or cardiological decompensation, with increased levels of proteinuria and blood pressure, as well as worsening cardiac function in patients with insufficiency. Studies have shown no association between the use of SARS inhibitors and a higher likelihood of contracting SARS-CoV-2 or developing Covid-19; there is data showing that SARS inhibitors improve clinical outcomes in hypertensive patients with Covid-19 6 .
- Patients taking specific medications at referral centers (such as Fabry's disease and atypical hemolytic-uremic syndrome [AHUS]) should continue treatment. Infusion centers must follow the protocols established by the Ministry of Health.
- According to new knowledge, severe and fatal cases may be more likely to develop thrombotic microangiopathy through pathogenic activation of the complement system 7 . Therefore, there is contraindication to change the dosage of eculizumab administration in patients using this medication, such as those with AHUS or paroxysmal nocturnal hemoglobinuria. A clinical study is even underway using complement inhibition as an alternative to treat Covid-19 8 .
- In all rare kidney diseases in which the patient uses specific medications for his treatment, it must be maintained in the recommended dosage schedule, unless there is any interaction with drugs used to treat Covid-19.
- Non-hormonal anti-inflammatory drugs (ibuprofen, diclofenac, ketoprofen, among others) should not be used due to the risk of acute kidney injury, use only dipyrone or paracetamol.

## Instructions on the interaction of medications used by the patient and medications that may be used in selected covid-19 cases.
There are several treatments being tested to treat Covid-19 and its complications. The physician seeing patients with rare kidney diseases needs to assess a possible interaction between the drugs routinely used by the patient and the drugs/treatments used to treat Covid-19.shows studies registered in the Clinical Trials for the treatment of Covid-19. - Remdesivir is a pre-drug, analogous to the nucleotide that inhibits viral RNA polymerase. The remdesivir triphosphate metabolite is the active form of the drug. Its effect has already been demonstrated in vitro against SARS-CoV-2. More recently, on May 1, 2020, the FDA approved the emergency use of remdesivir for treating severe cases of Covid-19 in adults and children, based on a review of key data from the study conducted by the National Institute of Health, with the compassionate use of remdesivir sponsored by Gilead, which analyzed different duration times of remdesivir. In its clinical trial, remdesivir reduced the duration of symptoms from 15 to 11 days (p = 0.001), and reduced mortality from 12% to 8% (p = 0.06). Ongoing, randomized and open studies, using remdesivir, may provide more data on the true role of this drug in the treatment of Covid-19.
Little is known about its interaction with immunosuppressive agents or other drugs; remdesivir is being used as a research drug, and there are still no pharmacokinetic studies in patients with impaired kidney or liver function. - Dexamethasone: Dexamethasone was one of the treatment arms of the Recovery initiative of Great Britain, which evaluated 11,500 patients.
In a preliminary analysis of the data before publication (press release), the researchers found a survival benefit in patients using dexamethasone. A total of 2,104 patients used dexamethasone

## Differential diagnosis
Do not forget about other flu-like syndromes that can potentially also be involved in the complement system activation, as in the case of the H1N1 influenza virus 15 .

## Vaccination schedule
It is recommended that patients keep the vaccination schedule up to date and receive the influenza vaccine.
collAboRAtoRs Lucimary Sylvestre, Fellype Barreto, Maria Izabel de Holanda, David Jose Machado, Valeria S P Veloso, Patricia Pontes and Gilson Bianchini.