Home Nephro News Rapid resolution of cytokine release syndrome and favorable clinical course of severe COVID-19 in a kidney transplant recipient treated with tocilizumab

Rapid resolution of cytokine release syndrome and favorable clinical course of severe COVID-19 in a kidney transplant recipient treated with tocilizumab

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Large image of Figure 1.

Immunomodulatory drugs hold promise for the management of cytokine release syndrome (CRS) in coronavirus disease-2019 (COVID-19) like tocilizumab (1x1Qin, C., Zhou, L., Hu, Z. et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;
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, 2x2Zhang, C., Wu, Z., Li, J.W. et al. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020;
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) However, its clinical utility in immunosuppressed patients is still lacking (3x3Rutherford, A.I., Subesinghe, S., Hyrich, K.L. et al. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;
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,4x4Fontana, F., Alfano, G., Mori, G. et al. Covid-19 pneumonia in a kidney transplant recipient successfully treated with Tocilizumab and Hydroxychloroquine. Am J Transplant. 2020;
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). Here, we describe the successful use of tocilizumab in a kidney transplant (KT) recipient with severe COVID-19.

A 69-year-old man received a KT in 2005 because of end-stage renal disease due to membranoproliferative glomerulonephritis complicated by chronic allograft nephropathy. Comorbidities included hypertension and obesity (body mass index: 31 kg/m2). Maintenance immunosuppression consisted of mycophenolic acid (1500 mg) and cyclosporine (120 mg). On April 2, 2020, he was admitted to our unit with dyspnea and hypoxia (blood oxygen saturation of 94% with an oxygen flow rate of 2 L/min). The RT-PCR test for SARS-CoV-2 detection was positive. There was also evidence of acute kidney injury (AKI) Kidney Disease: Improving Global Outcomes stage 1. Immunosuppression reduction consisted of mycophenolic acid withdrawal and reduced-dose cyclosporine. The patient was hydrated and antibiotic prophylaxis was started (Table 1). Unfortunately, the patient’s respiratory function further deteriorated and laboratory findings were suggestive of a CRS with a remarkably elevated (431 pg/mL) serum IL-6 levels. A single intravenous infusion of tocilizumab (8 mg/kg/day) was attempted. Two days after, oxygen was not longer required (Figure 1). The patient was discharged home and completed recovered from AKI.

Table 1Treatment approach and temporal course of clinical and laboratory parameters observed in the patient during hospitalization
Date April 2 April
4
April
5
April
6
April
7
April
9
April 10 April 11 April 13
Days from symptom onset 12 14 15 16 17 19 20 21 23
Highest recorded body temperature, °C 36.5 36.7 37.1 36.7 38.5 36.2 36.1 36.3 36.6
O2requirement, L/min 2 2 2 2.5 3 6 2 1 0
Percentage of lung infiltration on chest CT 25% 50%
Tocilizumab, 680 mg
Dexamethasone, 10 mg
Ceftriaxone
Azithromycin
Piperacillin-tazobactam
Serum creatinine, μmol/L 446 380 313 260 249 280 213
Serum albumin, g/L 37 34 32 34 36 31
C-reactive protein, mg/L 229 112 67 56 133 8.9
Procalcitonin, μg/L 5.05 1.02 0.65 0.14
Lactate dehydrogenase, U/L 243 348
High-sensitivity troponin, ng/L 43 42 44
IL-6, pg/mL 36.6 244.9 430.8 3.4
Fibrinogen, g/L 6.82 6.44 7.52 3.75
Ferritin, μg/L 857 745 861
D-dimer, μg/L 660 1060 1580
Lymphocytes, ×109/L 0.31 0.12 0.15 0.2 0.19 0.33 0.48
Hemoglobin, g/dL 10.2 8 7.1 9.8 10.3 9.8 10.3
Platelet count, ×109/L 229 198 171 182 196 164 121


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Figure 1

Temporal course of serum inflammatory biomarkers – C-reactive protein (CRP) and interleukin (IL)-6 – in relation to the patient’s need for oxygen therapy. The timing of tocilizumab infusion and dexamethasone are shown by the arrows.

Early detection of CRS biomarkers is recommended and should prompt anti-inflammatory interventions. Larger studies are needed to confirm the utility and safety of IL-6 inhibition combined with dexamethasone in KT recipients with COVID-19.

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