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. 2021 May 11;16(5):e0249760.
doi: 10.1371/journal.pone.0249760. eCollection 2021.

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients

Johanna Schneider  1 , Bernd Jaenigen  2 , Dirk Wagner  3 , Siegbert Rieg  3 , Daniel Hornuss  3 , Paul M Biever  3   4   5 , Winfried V Kern  3 , Gerd Walz  1
Affiliations

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients

Johanna Schneider et al. PLoS One. .

Abstract

Background: Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known.

Methods: We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients.

Results: In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597).

Conclusion: Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study design.
COVID-19, coronavirus disease-2019; ICU, intensive care unit; NEWS2, National Early Warning Score 2; triple therapy, therapy with lopinavir/ritonavir and hydroxychloroquine.
Fig 2
Fig 2. Lopinavir/ritonavir and hydroxychloroquine (triple therapy) are associated with an increase in the incidence of Acute Kidney Injury (AKI).
Association between triple therapy and AKI (A) in non-intensive care unit (ICU) patients and (B) ICU patients. P-values refer to the total number of AKI; RRT, renal replacement therapy. (C) Association between triple therapy and the maximum serum creatinine value.
See this image and copyright information in PMC

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