COVID-19 therapeutic options for patients with kidney disease
Authors: Hassan Izzedine, Kenar D. Jhaveri, Mark A. Perazella
Journal: Kidney International (2020)

Viral diseases are among the leading causes of morbidity and mortality in the world.1Andersen P.I. Ianevski A. Lysvand H. et al.Discovery and development of safe-in-man broad-spectrum antiviral agents.Int J Infect Dis. 2020; 93: 268-276Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar 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.2World Health OrganizationWHO 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-2020Google Scholar Given the race against time, identifying drug treatment options as soon as possible is critical to adequately respond to the COVID-19 outbreak.3Lu 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: 401-402Crossref PubMed Scopus (2136) Google Scholar 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,1Andersen P.I. Ianevski A. Lysvand H. et al.Discovery and development of safe-in-man broad-spectrum antiviral agents.Int J Infect Dis. 2020; 93: 268-276Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar 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,4Zhou P. Yang X.L. Wang X.G. et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; 579: 270-273Crossref PubMed Scopus (14613) Google Scholar 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.3Lu 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: 401-402Crossref PubMed Scopus (2136) Google Scholar 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.5Centers for Disease Control and PreventionChronic kidney disease in the United States, 2019.https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.htmlGoogle Scholar 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.6Guan W.J. Ni Z. Hu Y. et al.for the China Medical Treatment Expert Group for Covid-19Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20519) Google Scholar End-stage kidney disease patients are a highly susceptible group with an infection rate of 16%, which exceeds that observed in other populations.7Ma Y. Diao B. Lv X. et al.2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China.https://www.medrxiv.org/content/10.1101/2020.02.24.20027201v2Google Scholar 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 1Drug treatment options for COVID-19: potential kidney damage and dosage adjustment in CKD patientsCOVID-19 statusDosage according to glomerular filtration rateRenal adverse eventsNucleoside analogs FavipiravirPhase IINot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not reportedPotential mitochondrial toxicity RemdesivirPhase III GalidesivirAnimal AzvudinePhase II Ribavirin (in combination)Phase IIDosage adjustment according to standard recommendationDrug may be administered regardless of hemodialysis scheduleNot reportedHyperuricemia due to hemolytic anemiaNeuraminidase inhibitors Oseltamivir (in combination)Phase IVDosage adjustment according to standard recommendationDrug should be administered after dialysis session to avoid drug lossNot reportedFusion peptide inhibitor EK1Cell culture——HIV protease inhibitor Lopinavir/ritonavirPhase IV/IIIDrug should be administered at normal dosage and regardless of hemodialysis scheduleReversible AKI Danoprevir (in combination)Phase IVNot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not reported Darunavir + cobicistatPhase II/IIIDrug may be administered at normal dosage and regardless of hemodialysis scheduleNephrolithiasisFalse creatinine level increaseMembrane fusion inhibitor UmifenovirPhase IVNot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not reportedAminoquinoline family ChloroquinePhase IVDosage adjustment according to standard recommendationDrug should be administered after session on hemodialysis daysRenal lipidosis mimicking Fabry disease HydroxychloroquinePhase IIIRenal lipidosis mimicking Fabry diseaseFalse proteinuriaImmunotherapy CamrelizumabPhase IINot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not yet reportedPotential PDL-1 ligand-like renal toxicityMonoclonal antibodies AdalimumabPhase IVDrug should be administered at normal dosageaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Autoimmune GN (MN, IgA, lupus, ANCA vasculitis); granulomatous AIN TocilizumabPhase IVNot reported BevacizumabPhase II/IIIDrug should be administered at normal dosage and regardless of hemodialysis scheduleHT, proteinuria, TMA, GN, IN IFX-1 Anti C5aPhase IINot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not reported LeronlimabPhase II REGN-3048, REGN-3051Phase I VelocImmune (Regeneron Technology, Tarrytown, NY)Phase IOthers Tenofovir alafenamidePhase IVDosage adjustment according to standard recommendationDrug should be administered after dialysis sessionAKI; proximal renal tubular acidosis ThalidomidePhase IIHyperkalemia IgPhase II/IIIDrug should be administered at normal dosageIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis daysAKI; osmotic nephrosis PirfenidonePhase IIINot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.Not reported TranilastPhase IVNot reported FingolimodPhase IIDrug should be administered at normal dosage and regardless of hemodialysis scheduleTMA LeflunomidePhase IIIAnti-GBM GN; HT; tubular renal acidosis; TMA (in combination with methotrexate) Artemisinin piperaquinePhase IVNot availableaIn the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days.AKI; fatal acute hepatorenal failureCOVID-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.a In the absence of hemodialysis clearance data, drug should be administered after session on hemodialysis days. Open table in a new tab 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. 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. KDJ serves as a consultant for Astex Pharmaceuticals. All the other authors declared no competing interests. Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect acute kidney injury and other organ injury in critically ill patients with COVID-19Kidney InternationalVol. 98Issue 1PreviewWe read the letter by Izzedine et al.1 with great interest, especially the discussion of renal adverse effects of drug treatment options for coronavirus disease 2019 (COVID-19). We would like to draw particular attention to the potential adverse effect of chloroquine and hydroxychloroquine, the lysosomotropic antimalarial drugs that may inhibit the infection of severe acute respiratory syndrome coronavirus 2 by reducing the entry and replication of the virus. Severe acute respiratory syndrome coronavirus 2 enters cells via endocytosis by binding of its trimeric spike protein to cell surface receptors including angiotensin-converting enzyme 2. Full-Text PDF