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"Kidneys" Том 9, №2, 2020

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Management of patients on dialysis and with kidney transplant during COVID-19 coronavirus infection

Authors: Federico Alberici, Elisa Delbarba, Chiara Manenti, Laura Econimo, Francesca Valerio, Alessandra Pola, Camilla Maffei, Stefano Possenti, Paola Gaggia, Ezio Movilli, Sergio Bove, Fabio Malberti, Marco Farina, Martina Bracchi, Ester Maria Costantino, Nicola Bossini, Mario Gaggiotti, Francesco Scolari on behalf of the “Brescia Renal Covid Task Force”

Categories: Nephrology

Sections: Specialist manual

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Proposal for a therapeutic management plan for haemodialysis and transplant patients with COVID-19 infection
 

1. Asymptomatic/paucisymptomatic haemodialysis patients (fever > 37.5 °C but < 38°C, cough, cold WITHOUT dyspnoea) and negative chest X-ray 

Possible home management, if compatible with transport-related logistic management. The patient must wear a surgical mask at all times.
Antiviral therapy (duration: 5-20 days to be determined based on clinical progression)
— Lopinavir/ritonavir 200/50 mg 2 tabs x2/day OR
— Darunavir 800 mg 1 tab/day + ritonavir 100 mg 1 tab/day OR
— Darunavir/cobicistat 800/150 mg 1 tab/day
No adjustment for renal function necessary in any circumstances. Screen ongoing therapy for interactions (http://www.covid19-druginteractions.org/)
Hydroxychloroquinine
200 mg after each dialysis session (three times a week in patients on dialysis twice weekly).
Empirical antibiotic therapy
Only in the presence of bacterial superinfection.
Dialysis therapy 
In patients undergoing hemodiafiltration, continue the existing dialysis method. In patients undergoing dialysis, the use of the Theranova filter is recommended with the aim of increasing the efficiency of removal of middle size molecules and, therefore, inflammation mediators.

2. Asymptomatic/paucisymptomatic transplant patients (with mild symptoms: fever > 37.5 °C but < 38 °C, cough, cold WITHOUT dyspnoea) and negative chest X-ray

Hospitalization or home management, to be clinically decided on a case-by-case basis. Daily monitoring when at home, of fever and O2 saturation (if possible) with daily telephone visit by the transplant centre.
Immunosuppressive therapy:
— Stop MMF or azathioprine
— Stop calcineurin inhibitor
— Glucocorticoids: initiation of methylprednisolone 16 mg
Note: If progression is favourable, the timing of and methods for immunosuppressive therapy resumption are not yet clear and should be evaluated by carefully weighing the benefit-risk ratio in the individual patient.
Our proposed approach is to resume the calcineurin inhibitor at half of the previous dosage, starting at least 15 days after disappearance of symptoms and swab negativization, with the aim of gradually reaching a blood level of 3-5 ng/ml of tacrolimus and 200–300 ng/ml of cyclosporine at the second hour.
Further increase in the calcineurin inhibitor dosage should be considered after at least another 15 days with no symptoms and an additional negative swab. In the calcineurin inhibitor re-titration period, it is recommended to maintain the dose of methylprednisolone at 8–16 mg/day, based on clinical judgement. 
Case-by-case evaluation of subsequent re-initiation of MMF, azathioprine and m-TOR inhibitors 
Antiviral therapy (duration: 5-20 days to be determined based on clinical progression)
— Lopinavir/ritonavir 200/50 mg 2 tabs x2/day OR
— Darunavir 800 mg 1 tab/day+ ritonavir 100 mg 1 tab/day OR
— Darunavir/cobicistat 800/150 mg 1 tab/day
No adjustment for renal function necessary in any circumstances. Screen ongoing therapy for interactions (http://www.covid19-druginteractions.org/)
Hydroxychloroquinine
— 200 mg x2/day if GFR > 30 ml/min
— 200 mg/day if GFR > 15 ml/min and < 30 ml/min
— 200 mg every other day if GFR < 15 ml/min
Empirical antibiotic therapy
Only in the presence of bacterial superinfection

3. Haemodialysis patients with severe symptoms (fever > 38 °C, cough, dyspnoea) and/or positive chest X-ray

Hospitalization
Antiviral therapy (duration: 5–20 days to be determined based on clinical progression)
— Lopinavir/ritonavir 200/50 mg 2 tabs x2/day OR
— Darunavir 800 mg 1 tab/day + ritonavir 100 mg 1 tab/day OR
— Darunavir/cobicistat 800/150 mg 1 tab/day
No adjustment for renal function necessary in any circumstances. Screen ongoing therapy for interactions (http://www.covid19-druginteractions.org/)
Hydroxychloroquinine
200 mg every other day (three times a week in patients under dialysis twice weekly)
Empirical antibiotic therapy 
Only in the presence of bacterial superinfection
Dialysis therapy (quarantine area)
In patients undergoing hemodiafiltration, continue with the existing dialysis method. In patients undergoing dialysis, the use of the Theranova filter is recommended with the aim of increasing the efficiency of removal of middle size molecules and, therefore, inflammation mediators.

4. Transplanted patients with severe symptoms (fever >38 °C, cough, dyspnoea) and/or positive chest X-ray

Hospitalization
Immunosuppressive therapy:
— Stop MMF or azathioprine
— Stop calcineurin inhibitor
— Glucocorticoids: initiation of methylprednisolone 16 mg
Antiviral therapy (duration: 5-20 days to be determined based on clinical progression)
— Lopinavir/ritonavir 200/50 mg 2 tabs x2/day OR
— Darunavir 800 mg 1 tab/day + ritonavir 100 mg 1 tab/day OR
— Darunavir/cobicistat 800/150 mg 1 tab/day
No adjustment for renal function necessary in any circumstances. Screen ongoing therapy for іnteractions (http://www.covid19-druginteractions.org/)
Hydroxychloroquinine
— 200 mg x2/day if GFR > 30 ml/min
— 200 mg/day if GFR > 15 ml/min and < 30 ml/min
— 200 mg every other day if GFR < 15 ml/min
Empirical antibiotic therapy
Only in the presence of bacterial superinfection

5. Hospitalised (transplanted, dialysis) patient with clinical deterioration

If Brescia-COVID respiratory severity scale ≥ 2 (see appendix) AND IF, AT THE SAME TIME:
— The high viral load phase can be considered to be finished (e.g. no fever for > 72h and/or at least 7 days from symptoms onset)
— Ongoing superbacterial infection can be ruled out clinically
— There is ongoing worsening of respiratory exchanges and/or significant worsening of chest X-ray
Dexamethasone
20 mg/day for 5 days, thereafter 10 mg/day for 5 days.
Сonsider combination with Tocilizumab
In case of drug shortage, put cases with rapidly and significantly increasing of the D-Dimer levels first.
Requires in Italy signing of informed consent.

6. COVID-19 patients with Acute Kidney Injury (AKI) requiring continuous renal replacement therapy (CRRT)

Indication: patients with stage 3 AKI (defined as a 3-fold increase in creatinine levels from baseline or creatinine ≥ 4.0 mg/dl or defined based on amount of diuresis: diuresis < 0.3 ml/kg/h for ≥ 24 h or anuria for ≥ 12 h) hospitalized in ICU
Method: CVVH pre- and post-dilution with a prescribed dose > 25 ml/kg/h (to obtainan administered dose ≥ 25 ml/kg/h).
Anticoagulation
First choice: regional citrate anticoagulation (RCA).
Second choice: systemic heparinization with unfractionated heparin (UFH).
Third choice: treatment with no anticoagulants.
Note: most COVID-19-infected patients requiring intensive care management show altered liver function values secondary to drug-induced hepatotoxicity as well as due to possible liver involvement. This is associated with an increased risk for citrate accumulation.

7. COVID-19 patients with AKI requiring renal replacement therapy with haemodialysis

For AKI patients requiring intermittent haemodialysis, we recommend using the Theranova filter in order to increase the clearance of pro-inflammatory molecules.
Use of bilumen CVC is necessary to increase treatment efficiency. 
Переклад: проф. Д. Іванов, к.м.н. М.Д. Іванова


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