To the editor:
Viral diseases are among the leading causes of morbidity and mortality in the world.1 A novel coronavirus, designated as COVID-19, recently emerged in Wuhan, China, at the end of 2019. As of March 5, 2020, there are >95,000 reported cases of COVID-19 and >3,000 deaths wordwide.2 Given the race against time, identifying drug treatment options as soon as possible is critical to adequately respond to the COVID-19 outbreak.3
The “one drug, multiple viruses” paradigm came with the discovery of broad-spectrum antiviral agents, small molecules that inhibit a wide range of human viruses,1 and is even more pertinent today with outbreaks of Ebola, Zika, Dengue, influenza, and other viral infections, especially COVID-19. Because COVID-19 is 75% to 80% identical to the severe acute respiratory syndrome–CoV and even more closely related to several bat coronaviruses,4 potential treatment options against this emerging virus include as lopinavir/ritonavir, nucleoside analogues, neuraminidase inhibitors, remdesivir, fusion peptide (EK1), abidol, RNA synthesis inhibitors (such as tenofovir disoproxil fumarate [TDF], lamivudine [3TC]), interferon-α, and Chinese traditional medicine, such Shufengjiedu capsules and Lianhuaqingwen capsules, are. However, the efficacy and safety of these drugs for COVID-19 require confirmation by clinical experiments.3
Chronic kidney disease (CKD) is frequently encountered in the general population and is a risk for increased viral morbidity. According to the U.S. Centers for Disease Control and Prevention, approximately 15% of U.S. adults (37 million people) are estimated to have CKD.5 During the first 2 months of the current outbreak in China, CKD was reported in 4.3% of the Chinese patients infected with COVID-19 who had severe presentation.6 End-stage kidney disease patients are a highly susceptible group with an infection rate of 16%, which exceeds that observed in other populations.7
In the context of the epidemic or pandemic of COVID-19, these drugs will be prescribed to patients with CKD and/or end-stage kidney disease. Clinicians should thus be aware of the potential dosage adjustments and renal adverse events of those drugs in this patient group (Table 1 ).
Table 1.
COVID-19 status | Dosage according to glomerular filtration rate | Renal adverse events | |
---|---|---|---|
Nucleoside analogs | |||
Favipiravir | Phase II | Not availablea | Not reported Potential mitochondrial toxicity |
Remdesivir | Phase III | ||
Galidesivir | Animal | ||
Azvudine | Phase II | ||
Ribavirin (in combination) | Phase II | Dosage adjustment according to standard recommendation Drug may be administered regardless of hemodialysis schedule |
Not reported Hyperuricemia due to hemolytic anemia |
Neuraminidase inhibitors | |||
Oseltamivir (in combination) | Phase IV | Dosage adjustment according to standard recommendation Drug should be administered after dialysis session to avoid drug loss |
Not reported |
Fusion peptide inhibitor | |||
EK1 | Cell culture | — | — |
HIV protease inhibitor | |||
Lopinavir/ritonavir | Phase IV/III | Drug should be administered at normal dosage and regardless of hemodialysis schedule | Reversible AKI |
Danoprevir (in combination) | Phase IV | Not availablea | Not reported |
Darunavir + cobicistat | Phase II/III | Drug may be administered at normal dosage and regardless of hemodialysis schedule | Nephrolithiasis False creatinine level increase |
Membrane fusion inhibitor | |||
Umifenovir | Phase IV | Not availablea | Not reported |
Aminoquinoline family | |||
Chloroquine | Phase IV | Dosage adjustment according to standard recommendation Drug should be administered after session on hemodialysis days |
Renal lipidosis mimicking Fabry disease |
Hydroxychloroquine | Phase III | Renal lipidosis mimicking Fabry disease False proteinuria |
|
Immunotherapy | |||
Camrelizumab | Phase II | Not availablea | Not yet reported Potential PDL-1 ligand-like renal toxicity |
Monoclonal antibodies | |||
Adalimumab | Phase IV | Drug should be administered at normal dosagea | Autoimmune GN (MN, IgA, lupus, ANCA vasculitis); granulomatous AIN |
Tocilizumab | Phase IV | Not reported | |
Bevacizumab | Phase II/III | Drug should be administered at normal dosage and regardless of hemodialysis schedule | HT, proteinuria, TMA, GN, IN |
IFX-1 Anti C5a | Phase II | Not availablea | Not reported |
Leronlimab | Phase II | ||
REGN-3048, REGN-3051 | Phase I | ||
VelocImmune (Regeneron Technology, Tarrytown, NY) | Phase I | ||
Others | |||
Tenofovir alafenamide | Phase IV | Dosage adjustment according to standard recommendation Drug should be administered after dialysis session |
AKI; proximal renal tubular acidosis |
Thalidomide | Phase II | Hyperkalemia | |
Ig | Phase II/III | Drug should be administered at normal dosage In the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days |
AKI; osmotic nephrosis |
Pirfenidone | Phase III | Not availablea | Not reported |
Tranilast | Phase IV | Not reported | |
Fingolimod | Phase II | Drug should be administered at normal dosage and regardless of hemodialysis schedule | TMA |
Leflunomide | Phase III | Anti-GBM GN; HT; tubular renal acidosis; TMA (in combination with methotrexate) | |
Artemisinin piperaquine | Phase IV | Not availablea | AKI; fatal acute hepatorenal failure |
COVID-19, novel coronavirus disease 2019; AIN, acute interstitial nephritis; AKI, acute kidney injury; ANCA, antineutrophil cytoplasmic antibody; CKD, chronic kidney disease; GN, glomerulonephritis; GBM, glomerular basement membrane; HT, hypertension; IN, interstitial nephritis; MN, membranous nephropathy; PDL-1, programmed death ligand 1; TMA, thrombotic microangiopathy.
In the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.
Through this letter, we are not advocating any specific therapy and we support the notion that any therapy requires evaluation in a clinical trial. Furthermore, the rationale for providing this information to nephrologists is that we are likely to see off-label use of these drugs despite the absence of data, and we will need to provide input as to how the dosing should be modified in our patients with severely impaired kidney function.
Disclosure
KDJ serves as a consultant for Astex Pharmaceuticals. All the other authors declared no competing interests.
References
- 1.Andersen P.I., Ianevski A., Lysvand H. Discovery and development of safe-in-man broad-spectrum antiviral agents. Int J Infect Dis. 2020;93:268–276. doi: 10.1016/j.ijid.2020.02.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.World Health Organization WHO Director-General’s opening remarks at the media briefing on COVID-19—5 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---5-march-2020 Available at: Accessed March 7, 2020.
- 3.Lu H., Stratton C.W., Tang Y.W. Outbreak of pneumonia of unknown etiology in Wuhan China: the mystery and the miracle. J Med Virol. 2020;92:401–402. doi: 10.1002/jmv.25678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Zhou P., Yang X.L., Wang X.G. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. doi: 10.1038/s41586-020-2012-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Centers for Disease Control and Prevention Chronic kidney disease in the United States, 2019. https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html Available at: Accessed March 17, 2020.
- 6.Guan W.J., Ni Z., Hu Y., for the China Medical Treatment Expert Group for Covid-19 Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Ma Y., Diao B., Lv X. 2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China. https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2 Available at: Accessed March 30, 2020.