COVID-19 therapeutic options for patients with kidney disease

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.

Drug treatment options for COVID-19: potential kidney damage and dosage adjustment in CKD patients

	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.

^aIn 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.