Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PloS one - 16(2021), 5 vom: 11., Seite e0249760 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schneider, Johanna [VerfasserIn] |
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| Links: |
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| Themen: |
2494G1JF75 |
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| Anmerkungen: |
Date Completed 24.05.2021 Date Revised 03.11.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0249760 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM325261601 |
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| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Rieg, Siegbert |e verfasserin |4 aut | |
| 700 | 1 | |a Hornuss, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Biever, Paul M |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Winfried V |e verfasserin |4 aut | |
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