Use of tocilizumab in kidney transplant recipients with COVID-19

Abstract

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Keywords: clinical research/practice; infection and infectious agents - viral; kidney transplantation/nephrology; patient survival.

FIGURE 1

Percentage of patients with severe respiratory situation – defined as PaFi <300 or oxygen saturation <96% – at different points comparing patients who died and those who survived. Differences were found (P = .02) only at the time of admission. PaFi, arterial oxygen partial pressure/fraction of inspired oxygen **P < .01; TCZ, tocilizumab

FIGURE 2

Laboratory findings regarding coronavirus disease 2019 (COVID-19) infection evolution and tocilizumab (TCZ) use. Differences between alive and dead patients at 3 time points; admission, TCZ administration and 72 hours after TCZ. (A) Ferritin levels significantly increased in survivors along the inpatient stay. (B) Lactic acid dehydrogenase (LDH) levels increased after TCZ in patients who died and were significantly higher than in survivors at TCZ and after TCZ. (C) Procalcitonin decreased in survivors and levels after TCZ were higher in patients who died. (D) Interleukin-6 (IL-6), remained increased during admission, and the increase was especially relevant after TCZ treatment in patients who finally died. (E) D-dimer was significantly higher in those patients who died at TCZ and after TCZ, but levels increased along time in both subgroups. (F) C-reactive protein (CRP) initially increased and levels were similar between groups at TCZ treatment, however, although levels decreased after TCZ in all patients, survivors experienced a higher decrease. Continue lines represent comparisons at different time points in recipients who survived. Discontinue lines represent comparisons at different time points in those who died. Black asterisks regard to comparison between different time points and grey asterisks between dead and alive patients. *P < .05; **P < .01; ***P < .001