Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients.
Acute Kidney Injury
/ epidemiology
Aged
Antiviral Agents
/ adverse effects
COVID-19
/ virology
Creatinine
/ blood
Drug Therapy, Combination
Female
Germany
/ epidemiology
Humans
Hydroxychloroquine
/ adverse effects
Incidence
Intensive Care Units
Lopinavir
/ adverse effects
Male
Middle Aged
Retrospective Studies
SARS-CoV-2
/ isolation & purification
COVID-19 Drug Treatment
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
11
2020
accepted:
25
03
2021
entrez:
11
5
2021
pubmed:
12
5
2021
medline:
25
5
2021
Statut:
epublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 33974624
doi: 10.1371/journal.pone.0249760
pii: PONE-D-20-35907
pmc: PMC8112697
doi:
Substances chimiques
Antiviral Agents
0
Lopinavir
2494G1JF75
Hydroxychloroquine
4QWG6N8QKH
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0249760Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
Lancet Infect Dis. 2005 Mar;5(3):147-55
pubmed: 15766649
JAMA. 2020 Apr 28;323(16):1612-1614
pubmed: 32191259
Kidney Int. 2020 May;97(5):829-838
pubmed: 32247631
Nephron Clin Pract. 2012;120(4):c179-84
pubmed: 22890468
Kidney Int. 2020 Jul;98(1):219-227
pubmed: 32327202
Antimicrob Agents Chemother. 1998 Dec;42(12):3218-24
pubmed: 9835517
J Pharmacol Exp Ther. 2018 Jun;365(3):447-459
pubmed: 29438998
Resuscitation. 2021 Feb;159:150-157
pubmed: 33176170
AIDS. 2007 Jan 2;21(1):119-20
pubmed: 17148983
Lancet Respir Med. 2020 May;8(5):475-481
pubmed: 32105632
World J Clin Cases. 2019 Dec 26;7(24):4377-4383
pubmed: 31911921
J Am Soc Nephrol. 2003 Apr;14(4):1022-30
pubmed: 12660337
Clin Kidney J. 2013 Oct;6(5):533-6
pubmed: 26120446
J Infect Dis. 2013 May 1;207(9):1359-69
pubmed: 23382571
J Am Soc Nephrol. 2020 Sep;31(9):2158-2167
pubmed: 32727719
Drugs. 2006;66(9):1275-99
pubmed: 16827606
Am J Med. 1997 Nov;103(5):368-75
pubmed: 9375704
Clin Infect Dis. 2020 Jul 28;71(15):732-739
pubmed: 32150618
J Infect Dis. 2015 Dec 15;212(12):1904-13
pubmed: 26198719
AIDS. 2015 Sep 10;29(14):1831-6
pubmed: 26372389
Nat Commun. 2020 Mar 30;11(1):1600
pubmed: 32231244
Pharm Res. 2004 Sep;21(9):1622-30
pubmed: 15497688
Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):456-465
pubmed: 30346663
Clin Pharmacol Ther. 2020 Oct;108(4):791-797
pubmed: 32324898
Br J Pharmacol. 2020 Nov;177(21):4813-4824
pubmed: 32329520
Drugs. 2003;63(8):769-802
pubmed: 12662125
Am J Kidney Dis. 2008 Oct;52(4):699-705
pubmed: 18585835
Antimicrob Agents Chemother. 2009 Apr;53(4):1468-75
pubmed: 19188392
BMJ. 2020 Mar 26;368:m1091
pubmed: 32217556
Nat Rev Nephrol. 2020 Jun;16(6):308-310
pubmed: 32273593
BMJ. 2020 Jul 30;370:m2980
pubmed: 32732190