Cyclosporine as a preferred calcineurin inhibitor in renal allograft recipients with COVID-19 infection

To the editor:

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. ¹ report withdrawal of baseline immunosuppression in 20 patients with COVID-19 pneumonia and mainly continuation with methylprednisolone, Banerjee et al. ² 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 editorial³ 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.⁴ 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.²): clinical characteristics, outcome, and blood parameters of first kidney transplant patient converted to cyclosporine during COVID-19 infection

Patient	Age/sex	Tx date	Comorbidities	Respiratory and renal involvement	Baseline creatinine (eGFR ml/min per 1.73 m2)	Baseline immunosuppression and treatment	ACEI or ARB	Outcome
1	45 yr/M	2004	HT/ hypercholisterinemia	Yes, ARDS + AKI (without need for RRT)	124–141 (51–59)	MMF MMF stopped and switch to CyA/Pred	No	Discharged from ITU, now at home, full recovery

Cont. with patient	White 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)
1	7.4 (D1)	1.18 (D4)	18 (D1), 289 (D8)	2563 (D9)	600 (D2), 8800 (D10)	346 (D2), 634 (D9)	<13

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.