Cyclosporine as a preferred calcineurin inhibitor in renal allograft recipients with COVID-19 infection
Authors: Stephan Kemmner, Markus O. Guba, Ulf Schönermarck, Manfred Stangl, Michael Fischereder
Journal: Kidney International (2020)

Kidney International recently published 2 series of renal allograft recipients with coronavirus disease 2019 (COVID-19) infection including different approaches to maintenance immunosuppression. Although Alberici et al.1Alberici F. Delbarba E. Manenti C. et al.A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia.Kidney Int. 2020; 97: 1083-1088Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar report withdrawal of baseline immunosuppression in 20 patients with COVID-19 pneumonia and mainly continuation with methylprednisolone, Banerjee et al.2Banerjee D. Popoola J. Shah S. et al.COVID-19 infection in kidney transplant recipients.Kidney Int. 2020; 97: 1076-1082Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar pursued more-gentle reduction of immunosuppression with mainly discontinuation of the antimetabolite in 7 patients with COVID-19 infections of varying severity. However, in 2 of the 7 patients, the calcineurin inhibitor tacrolimus was additionally stopped because of severe respiratory distress syndrome. The corresponding editorial3Coates P.T. Wong G. Drueke T. et al.Early experience with COVID-19 in kidney transplantation.Kidney Int. 2020; 97: 1074-1075Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar suggests switching to the calcineurin inhibitor cyclosporine as a possible further approach for future exploration, as in vitro data report suppression of viral replication for various coronaviruses at noncytotoxic concentrations regardless of immunosuppressive effects of cyclosporine.4de Wilde A.H. Zevenhoven-Dobbe J.C. van der Meer Y. et al.Cyclosporin A inhibits the replication of diverse coronaviruses.J Gen Virol. 2011; 92: 2542-2548Crossref PubMed Scopus (199) Google Scholar In line with this suggestion, we report the first renal allograft recipient converted to cyclosporine during COVID-19 infection. The 45-year-old male had been transplanted 16 years ago. His immunosuppression consisted of only the antimetabolite mycophenolate mofetil. On admission, the patient presented with typical symptoms of COVID-19 pneumonia including fever, cough, dyspnea, and crazy paving pattern in computed tomography scan. The main characteristics are summarized in Table 1. The therapeutic regimen consisted of withdrawal of the antimetabolite, conversion to low-dose steroid, and introduction of low-dose cyclosporine, azithromycin, and hydroxychloroquine. He required mechanical ventilation for 4 days until his general condition improved significantly, and he was able to be discharged after 17 days with stable allograft function. Therefore, switching to a cyclosporine-based immunosuppression may represent another therapeutic option in the case of COVID-19 infection following kidney transplantation.Table 1(According to Banerjee et al.2Banerjee D. Popoola J. Shah S. et al.COVID-19 infection in kidney transplant recipients.Kidney Int. 2020; 97: 1076-1082Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar): clinical characteristics, outcome, and blood parameters of first kidney transplant patient converted to cyclosporine during COVID-19 infectionPatientAge/sexTx dateComorbiditiesRespiratory and renal involvementBaseline creatinine (eGFR ml/min per 1.73 m2)Baseline immunosuppression and treatmentACEI or ARBOutcome145 yr/M2004HT/ hypercholisterinemiaYes, ARDS + AKI (without need for RRT)124–141 (51–59)MMFMMF stopped and switch to CyA/PredNoDischarged from ITU,now at home,full recoveryCont. with patientWhite cell count (×109 /l) (3.9–9.8)Lymphocyte count (×109 /l) (1.1–3.2)Serum CRP (mg/l) (<5)Serum ferritin (μg/l) (30–400)Serum D dimer (μg/l) (0–500)Serum LDH (U/l) (<249)Serum troponin T (ng/l) (<14)17.4 (D1)1.18 (D4)18 (D1),289 (D8)2563 (D9)600 (D2),8800 (D10)346 (D2),634 (D9)<13ACEI, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ARDS, acute respiratory distress syndrome; Cont., continued; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; CyA, cyclosporine A; D, day after admission; D1, day of admission; eGFR, estimated glomerular filtration rate; HT, hypertension; ITU, intensive therapy unit; LDH, lactate dehydrogenase; M, male; MMF, mycophenolate mofetil; Pred, prednisolone; RRT, renal replacement therapy; Tx, treatment. Open table in a new tab ACEI, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ARDS, acute respiratory distress syndrome; Cont., continued; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; CyA, cyclosporine A; D, day after admission; D1, day of admission; eGFR, estimated glomerular filtration rate; HT, hypertension; ITU, intensive therapy unit; LDH, lactate dehydrogenase; M, male; MMF, mycophenolate mofetil; Pred, prednisolone; RRT, renal replacement therapy; Tx, treatment. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumoniaKidney InternationalVol. 97Issue 6PreviewThe outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 years [inter quartile range 51-64 years], median age of transplant 13 years [9-20 years], baseline eGFR 36.5 [23-47.5]) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. Full-Text PDF Open AccessCOVID-19 infection in kidney transplant recipientsKidney InternationalVol. 97Issue 6PreviewBy 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. Full-Text PDF Open AccessEarly experience with COVID-19 in kidney transplantationKidney InternationalVol. 97Issue 6PreviewIn this edition of Kidney International, we publish 2 series of patients who had undergone kidney transplantation during the coronavirus disease 2019 (COVID-19) pandemic that have taken different approaches to transplant immunosuppressive therapy and antiviral treatment in the early days of the developing pandemic in the United Kingdom and Italy. The first series of 7 cases of COVID-19 infection in patients who had undergone kidney transplantation comes from St. George's, St. Helier's, and King's College Hospitals in south London, United Kingdom,1 and the second series of 20 cases originates from Spedali Civili University Hospital in Brescia, Italy. Full-Text PDF Open Access