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?:abstract
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A 58-year-old man developed reversible acute kidney injury (AKI) following concomitant administration of tacrolimus with off-label darunavir, ritonavir and hydroxychloroquine He also developed COVID-19 pneumonia following immunosuppressive drug therapy with tacrolimus, prednisolone and mycophenolate-mofetil His COVID-19 pneumonia was further treated with off-label azithromycin, darunavir, favipiravir, hydroxychloroquine and ritonavir [routes and durations of treatments to reactions onsets not stated;not all outcomes and dosages stated] The man presented with acute fever, watery diarrhoea, nausea and dyspnea Two years before presentation, he had undergone a kidney transplantation His medical history also included dyslipidaemia, hypertension and post-transplant diabetes mellitus After receiving induction therapy, he had been undergoing maintenance therapy with tacrolimus 2 5 mg/d, mycophenolate mofetil 2 mg/d and prednisolone and 2 5 mg/ During the course of treatment, he had developed cytomegalovirus (CMV) viremia treated with ganciclovir and valganciclovir He was additionally receiving various other concomitant medications On 13 March 2020, 12 days before presentation, he had developed diarrhea which continued throughout with additional fever, myalgia, dry cough and shortness of breath Upon his presentation, his body temperature was 39 2°C, BP was 118/65mm Hg, respiratory rate was 24 times/minutes, oxygen saturation on room air was 94% and pulse rate was 92 beats/minute He underwent nasal swab testing and stool testing, which was positive for COVID-19 His chest radiograph showed bilateral multifocal patchy infiltration pneumonia His immunosuppressive drug therapy was thought to contribute in the development of COVID-19 pneumonia, with atypical presentations of diarrhoea and nausea The man started receiving off-label treatment with azithromycin, hydroxychloroquine, darunavir, ritonavir and favipiravir 3 2 g/d (subsequently lowered to 1 2 g/d) on the first day of hospitalisation His tacrolimus dose was lowered to 1 5 mg/d, whereas mycophenolate mofetil was discontinued on day 3 Hence, his prednisolone was continued at an increased dose of 15 mg/d from day 3 He was also initiated on prophylactic ceftriaxone for bacterial infection He was then transferred to another hospital and received oxygen therapy to maintain adequate oxygenation During this admission, his laboratory examinations were significant for lymphopenia, elevated levels of creatine, serum sodium and interleukin 6 (IL-6) His tacrolimus trough levels were also found to be elevated and tacrolimus was discontinued, as were hydroxychloroquine, darunavir, ritonavir A diagnosis of AKI secondary to raised tacrolimus trough levels, due to an interaction with anti-virals was considered On days 4-5 of admission (day 11-12 of fever), his lymphocyte count and PaO2/FiO2 ratio decreased A chest radiography showed increased bilateral infiltration and he underwent placement of a high-flow oxygen nasal cannula He was then treated with immunoglobulin and underwent haemoperfusion for increased level of endotoxin On hospital day 6, his IL-6 levels had increased further and he received tocilizumab Within 4 days of initiating tocilizumab, his clinical condition improved and he did not require oxygen therapy Subsequent chest radiography showed reduced infiltration However, in spite of early discontinuation of tacrolimus and anti-viral medications, his tacrolimus trough levels remained high;his tacrolimus had been withdrawn since 10 days until the tacrolimus trough levels and creatinine returned to baseline Eventually, COVID-19 was undetectable and his lymphopenia resolved, following which, mycophenolate-mofetil was reintroduced
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