Safety profile of azvudine in COVID-19 patients with renal impairment: a retrospective analysis
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2026.1830085, Jun 2026
Azvudine for COVID-19
No treatment is 100% effective.
Protocols combine treatments.
Retrospective 328 hospitalized COVID-19 patients in China showing higher risk of adverse drug events with azvudine in patients with renal impairment.
Zhang et al., 29 Jun 2026, retrospective, China, peer-reviewed, 6 authors.
Contact: huang_sc@bitzh.edu.cn, wen_zl@bitzh.edu.cn.
Abstract:
OPEN ACCESS
EDITED BY Ursula Gundert-Remy, Charité University Medicine Berlin, Germany
REVIEWED BY Daniele Mengato, University Hospital of Padua, Italy Marios Spanakis,
University of Crete, Greece
*CORRESPONDENCE Sichao Huang, huang\_sc@bitzh.edu.cn Zhiyong Wen,
[wen\_zl@bitzh.edu.cn](mailto:wen_zl@bitzh.edu.cn)
† These authors have contributed equally to this work and share first authorship
RECEIVED 13 March 2026 REVISED 24 May 2026 ACCEPTED 26 May 2026 PUBLISHED 29 June 2026
CITATION
Zhang X, Qian J, Cui J, Luo Y, Huang S and Wen Z (2026) Safety profile of azvudine in COVID-19 patients with renal impairment: a retrospective analysis.
Front. Pharmacol. 17:1830085.
doi: 10.3389/fphar.2026.1830085
COPYRIGHT
© 2026 Zhang, Qian, Cui, Luo, Huang and Wen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
TYPE Original Research PUBLISHED 29 June 2026 DOI 10.3389/fphar.2026.1830085
[Safety profile of azvudine in COVID-19 patients with renal impairment: a retrospective analysis](https://www.frontiersin.org/articles/10.3389/fphar.2026.1830085/full)
Xiaomin Zhang 1† , Jiajian Qian 2† , Jiawen Cui 3† , Yuhong Luo 2 , Sichao Huang 2 * and Zhiyong Wen 2 *
1 Department of Pharmacy, The Fifth Affiliated Hospital of Zunyi Medical, University, Zhuhai (Zhuhai Sixth People's Hospital), Zhuhai, China, 2 Department of Pharmacy, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China, 3 Department of Pharmacy, Guangzhou Twelfth People's Hospital, Guangzhou, China
Objective: Azvudine (FNC), an antiviral drug approved in China for the treatment of Coronavirus disease 2019 (COVID-19) infection, has not yet established a welldefined safety profile in patients with renal impairment. This study aimed to evaluate the safety of using FNC in patients with renal impairment.
Methods: We conducted a retrospective analysis of clinical data from 328 COVID19 patients to assess FNC-related adverse drug events (ADEs). Patients were stratified into two cohorts: a control group with an estimated glomerular filtration rate (eGFR) > 70 mL/min/1.73 m 2 and a study group with eGFR ≤ 70 mL/min/ 1.73 m 2 . Our main objective was to assess whether there were any differences in the incidence of ADEs between the two groups. Secondly, we attempted to develop predictive models for ADEs that were frequent and closely related to the eGFR grade.
Results: Over half of the cohort (51.8%) experienced FNC-associated ADEs, predominantly hepatic function abnormalities (36.6%) and renal function abnormalities (18.9%). The incidence of acute kidney injury (AKI) was 8.8%. Patients with renal impairment exhibited a higher risk of ADEs, particularly among elderly individuals and patients with a high neutrophil count. No differences in hepatic function abnormalities were found between the two groups. Patients with renal impairment had a higher risk of renal function abnormalities and AKI, with ..
DOI record:
{
"DOI": "10.3389/fphar.2026.1830085",
"ISSN": [
"1663-9812"
],
"URL": "http://dx.doi.org/10.3389/fphar.2026.1830085",
"abstract": "<jats:sec>\n <jats:title>Objective</jats:title>\n <jats:p>Azvudine (FNC), an antiviral drug approved in China for the treatment of Coronavirus disease 2019 (COVID-19) infection, has not yet established a well-defined safety profile in patients with renal impairment. This study aimed to evaluate the safety of using FNC in patients with renal impairment.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>\n We conducted a retrospective analysis of clinical data from 328 COVID-19 patients to assess FNC-related adverse drug events (ADEs). Patients were stratified into two cohorts: a control group with an estimated glomerular filtration rate (eGFR) &gt; 70 mL/min/1.73 m\n <jats:sup>2</jats:sup>\n and a study group with eGFR ≤70 mL/min/1.73 m\n <jats:sup>2</jats:sup>\n . Our main objective was to assess whether there were any differences in the incidence of ADEs between the two groups. Secondly, we attempted to develop predictive models for ADEs that were frequent and closely related to the eGFR grade.\n </jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Over half of the cohort (51.8%) experienced FNC-associated ADEs, predominantly hepatic function abnormalities (36.6%) and renal function abnormalities (18.9%). The incidence of acute kidney injury (AKI) was 8.8%. Patients with renal impairment exhibited a higher risk of ADEs, particularly among elderly individuals and patients with a high neutrophil count. No differences in hepatic function abnormalities were found between the two groups. Patients with renal impairment had a higher risk of renal function abnormalities and AKI, with decreased eGFR identified as an independent risk factor for these ADEs. The predictors included in the nomogram model for AKI were neutrophil count and eGFR grade. The nomogram model demonstrated predictive performance and calibration, with an area under the curve of 0.812.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>These findings highlight the need for enhanced safety monitoring and potential dose adjustments when administering FNC to COVID-19 patients with renal impairment.</jats:p>\n </jats:sec>",
"alternative-id": [
"10.3389/fphar.2026.1830085"
],
"article-number": "1830085",
"author": [
{
"affiliation": [
{
"name": "Department of Pharmacy, The Fifth Affiliated Hospital of Zunyi Medical, University, Zhuhai (Zhuhai Sixth People’s Hospital)",
"place": [
"Zhuhai, China"
]
}
],
"family": "Zhang",
"given": "Xiaomin",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "first"
},
{
"affiliation": [
{
"name": "Department of Pharmacy, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)",
"place": [
"Zhuhai, China"
]
}
],
"family": "Qian",
"given": "Jiajian",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Pharmacy, Guangzhou Twelfth People’s Hospital",
"place": [
"Guangzhou, China"
]
}
],
"family": "Cui",
"given": "Jiawen",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Pharmacy, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)",
"place": [
"Zhuhai, China"
]
}
],
"family": "Luo",
"given": "Yuhong",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Pharmacy, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)",
"place": [
"Zhuhai, China"
]
}
],
"family": "Huang",
"given": "Sichao",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Pharmacy, Zhuhai People’s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)",
"place": [
"Zhuhai, China"
]
}
],
"family": "Wen",
"given": "Zhiyong",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
}
],
"container-title": "Frontiers in Pharmacology",
"container-title-short": "Front. Pharmacol.",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"frontiersin.org"
]
},
"created": {
"date-parts": [
[
2026,
6,
29
]
],
"date-time": "2026-06-29T05:40:45Z",
"timestamp": 1782711645000
},
"deposited": {
"date-parts": [
[
2026,
6,
29
]
],
"date-time": "2026-06-29T05:40:46Z",
"timestamp": 1782711646000
},
"indexed": {
"date-parts": [
[
2026,
6,
29
]
],
"date-time": "2026-06-29T05:48:05Z",
"timestamp": 1782712085702,
"version": "3.54.5"
},
"is-referenced-by-count": 0,
"issued": {
"date-parts": [
[
2026,
6,
29
]
]
},
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
6,
29
]
],
"date-time": "2026-06-29T00:00:00Z",
"timestamp": 1782691200000
}
}
],
"link": [
{
"URL": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1830085/full",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1965",
"original-title": [],
"prefix": "10.3389",
"published": {
"date-parts": [
[
2026,
6,
29
]
]
},
"published-online": {
"date-parts": [
[
2026,
6,
29
]
]
},
"publisher": "Frontiers Media SA",
"reference": [
{
"DOI": "10.1124/dmd.122.000967",
"article-title": "Emerging roles of uremic toxins and inflammatory cytokines in the alteration of hepatic drug disposition in patients with kidney dysfunction",
"author": "Arakawa",
"doi-asserted-by": "publisher",
"first-page": "1127",
"journal-title": "Drug Metab. Dispos.",
"key": "B1",
"volume": "51",
"year": "2023"
},
{
"DOI": "10.1136/flgastro-2021-101886",
"article-title": "Guideline review: EASL clinical Practice Guidelines: drug-induced liver injury (DILI)",
"author": "Brennan",
"doi-asserted-by": "publisher",
"first-page": "332",
"journal-title": "Frontline Gastroenterol.",
"key": "B2",
"volume": "13",
"year": "2021"
},
{
"DOI": "10.1021/acs.accounts.1c00697",
"article-title": "4'-Modified nucleosides for antiviral drug discovery: achievements and perspectives",
"author": "Chang",
"doi-asserted-by": "publisher",
"first-page": "565",
"journal-title": "Acc. Chem. Res.",
"key": "B3",
"volume": "55",
"year": "2022"
},
{
"DOI": "10.1016/j.heliyon.2023.e20153",
"article-title": "Efficacy and safety of azvudine in patients with COVID-19: a systematic review and meta-analysis",
"author": "Chen",
"doi-asserted-by": "publisher",
"first-page": "e20153",
"journal-title": "Heliyon",
"key": "B4",
"volume": "9",
"year": "2023"
},
{
"DOI": "10.1016/j.gendis.2023.101115",
"article-title": "Mitochondrial dysfunction: a promising therapeutic target for liver diseases",
"author": "Chen",
"doi-asserted-by": "publisher",
"first-page": "101115",
"journal-title": "Genes Dis.",
"key": "B5",
"volume": "11",
"year": "2023"
},
{
"DOI": "10.1080/0886022X.2024.2392883",
"article-title": "Effect of chronic kidney disease on adverse drug reactions to anti-tubercular treatment: a retrospective cohort study",
"author": "Datta",
"doi-asserted-by": "publisher",
"first-page": "2392883",
"journal-title": "Ren. Fail.",
"key": "B6",
"volume": "46",
"year": "2024"
},
{
"DOI": "10.1016/j.jhep.2009.04.009",
"article-title": "EASL Clinical practice Guidelines: management of cholestatic liver diseases",
"doi-asserted-by": "publisher",
"first-page": "237",
"journal-title": "J. Hepatol.",
"key": "B7",
"volume": "51",
"year": "2009"
},
{
"DOI": "10.3389/fonc.2022.820647",
"article-title": "FNC: an advanced anticancer therapeutic or just an underdog?",
"author": "Fayzullina",
"doi-asserted-by": "publisher",
"first-page": "820647",
"journal-title": "Front. Oncol.",
"key": "B8",
"volume": "12",
"year": "2022"
},
{
"DOI": "10.1038/s41591-019-0675-0",
"article-title": "Chronic inflammation in the etiology of disease across the life span",
"author": "Furman",
"doi-asserted-by": "publisher",
"first-page": "1822",
"journal-title": "Nat. Med.",
"key": "B9",
"volume": "25",
"year": "2019"
},
{
"DOI": "10.1016/S0140-6736(20)30183-5",
"article-title": "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China",
"author": "Huang",
"doi-asserted-by": "publisher",
"first-page": "497",
"journal-title": "Lancet",
"key": "B10",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1186/s12967-022-03767-z",
"article-title": "Innate immunity, cytokine storm, and inflammatory cell death in COVID-19",
"author": "Karki",
"doi-asserted-by": "publisher",
"first-page": "542",
"journal-title": "J. Transl. Med.",
"key": "B11",
"volume": "20",
"year": "2022"
},
{
"DOI": "10.1186/cc11454",
"article-title": "Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1)",
"author": "Kellum",
"doi-asserted-by": "publisher",
"first-page": "204",
"journal-title": "Crit. Care.",
"key": "B12",
"volume": "17",
"year": "2013"
},
{
"DOI": "10.1053/j.ajkd.2023.09.012",
"article-title": "Kidney function decline and serious adverse drug reactions in patients with CKD",
"author": "Laville",
"doi-asserted-by": "publisher",
"first-page": "601",
"journal-title": "Am. J. Kidney Dis.",
"key": "B13",
"volume": "83",
"year": "2024"
},
{
"DOI": "10.3389/fimmu.2023.1151937",
"article-title": "TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver",
"author": "Lucke",
"doi-asserted-by": "publisher",
"first-page": "1151937",
"journal-title": "Front. Immunol.",
"key": "B14",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.3122/jabfm.2013.05.130012",
"article-title": "The prevalence of chronic diseases and multimorbidity in primary care practice: a PPRNet report",
"author": "Ornstein",
"doi-asserted-by": "publisher",
"first-page": "518",
"journal-title": "J. Am. Board Fam. Med.",
"key": "B15",
"volume": "26",
"year": "2013"
},
{
"DOI": "10.2215/CJN.13820820",
"article-title": "Outcomes of COVID-19 in CKD patients: a multicenter electronic medical record cohort Study",
"author": "Pakhchanian",
"doi-asserted-by": "publisher",
"first-page": "785",
"journal-title": "Clin. J. Am. Soc. Nephrol.",
"key": "B16",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1155/2017/6193694",
"article-title": "Oxidative stress and acute kidney Injury in critical illness: Pathophysiologic Mechanisms-Biomarkers-Interventions, and future perspectives",
"author": "Pavlakou",
"doi-asserted-by": "publisher",
"first-page": "6193694",
"journal-title": "Oxid. Med. Cell. Longev.",
"key": "B17",
"volume": "2017",
"year": "2017"
},
{
"DOI": "10.1186/s12879-025-10643-w",
"article-title": "Real-world effectiveness and safety of oral Azvudine versus Paxlovid for COVID-19 in patients with kidney disease: a multicenter, retrospective, cohort study",
"author": "Rao",
"doi-asserted-by": "publisher",
"first-page": "275",
"journal-title": "Bmc. Infect. Dis.",
"key": "B18",
"volume": "25",
"year": "2025"
},
{
"DOI": "10.4110/in.2018.18.e27",
"article-title": "Damage-Associated molecular patterns in inflammatory diseases",
"author": "Roh",
"doi-asserted-by": "publisher",
"first-page": "e27",
"journal-title": "Immune Netw.",
"key": "B19",
"volume": "18",
"year": "2018"
},
{
"DOI": "10.1152/ajprenal.00195",
"article-title": "Immune cells and inflammation in AKI to CKD progression",
"author": "Sato",
"doi-asserted-by": "publisher",
"first-page": "F1501",
"journal-title": "Am. J. Physiol. Ren. Physiol.",
"key": "B20",
"volume": "315",
"year": "2018"
},
{
"DOI": "10.1002/jmv.29007",
"article-title": "Azvudine therapy of common COVID-19 in hemodialysis patients",
"author": "Shang",
"doi-asserted-by": "publisher",
"first-page": "e29007",
"journal-title": "J. Med. Virol.",
"key": "B21",
"volume": "95",
"year": "2023"
},
{
"DOI": "10.1021/acs.jmedchem.0c00940",
"article-title": "Mechanistic Insight into antiretroviral potency of 2'-Deoxy-2'-beta-fluoro-4'-azidocytidine (FNC) with a long-lasting effect on HIV-1 prevention",
"author": "Sun",
"doi-asserted-by": "publisher",
"first-page": "8554",
"journal-title": "J. Med. Chem.",
"key": "B22",
"volume": "63",
"year": "2020"
},
{
"DOI": "10.1001/jamainternmed.2017.1938",
"article-title": "Association of adverse events With antibiotic use in hospitalized patients",
"author": "Tamma",
"doi-asserted-by": "publisher",
"first-page": "1308",
"journal-title": "JAMA Intern. Med.",
"key": "B23",
"volume": "177",
"year": "2017"
},
{
"DOI": "10.1016/j.jamda.2017.12.002",
"article-title": "Research priorities for optimizing geriatric pharmacotherapy: an international consensus",
"author": "Tan",
"doi-asserted-by": "publisher",
"first-page": "193",
"journal-title": "J. Am. Med. Dir. Assoc.",
"key": "B24",
"volume": "19",
"year": "2018"
},
{
"DOI": "10.1080/1040841X.2024.2384885",
"article-title": "Damage-associated molecular patterns in viral infection: potential therapeutic targets",
"author": "Tian",
"doi-asserted-by": "publisher",
"first-page": "514",
"journal-title": "Crit. Rev. Microbiol.",
"key": "B25",
"volume": "51",
"year": "2025"
},
{
"DOI": "10.1371/journal.pone.0105617",
"article-title": "Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro",
"author": "Wang",
"doi-asserted-by": "publisher",
"first-page": "e105617",
"journal-title": "PLoS One",
"key": "B26",
"volume": "9",
"year": "2014"
},
{
"DOI": "10.3389/fphar.2022.1043836",
"article-title": "Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes",
"author": "Wang",
"doi-asserted-by": "publisher",
"first-page": "1043836",
"journal-title": "Front. Pharmacol.",
"key": "B27",
"volume": "13",
"year": "2022"
},
{
"DOI": "10.2174/1389200224666230509104404",
"article-title": "Physiologically based pharmacokinetic model for older adults and Its application in geriatric drug research",
"author": "Wu",
"doi-asserted-by": "publisher",
"first-page": "211",
"journal-title": "Curr. Drug Metab.",
"key": "B28",
"volume": "24",
"year": "2023"
},
{
"DOI": "10.1038/s41392-020-00351-z",
"article-title": "Azvudine (FNC): a promising clinical candidate for COVID-19 treatment",
"author": "Yu",
"doi-asserted-by": "publisher",
"first-page": "236",
"journal-title": "Signal Transduct. Target. Ther.",
"key": "B29",
"volume": "5",
"year": "2020"
},
{
"DOI": "10.1002/VIW.20240075",
"article-title": "The effectiveness and safety of azvudine treatment in COVID-19 patients with kidney disease based on a multicenter retrospective cohort study",
"author": "Yu",
"doi-asserted-by": "publisher",
"first-page": "20240075",
"journal-title": "VIEW",
"key": "B30",
"volume": "6",
"year": "2025"
},
{
"DOI": "10.1038/s41392-021-00835-6",
"article-title": "Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients",
"author": "Zhang",
"doi-asserted-by": "publisher",
"first-page": "414",
"journal-title": "Signal Transduct. Target. Ther.",
"key": "B31",
"volume": "6",
"year": "2021"
},
{
"DOI": "10.3760/cma.j.issn.1674-2397.2023.01.002",
"article-title": "Expert consensus on antiviral therapy of COVID-19",
"author": "Zhang",
"doi-asserted-by": "publisher",
"first-page": "10",
"journal-title": "Chin. J. Clin. Infect. Dis.",
"key": "B32",
"volume": "16",
"year": "2023"
}
],
"reference-count": 32,
"references-count": 32,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1830085/full"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Safety profile of azvudine in COVID-19 patients with renal impairment: a retrospective analysis",
"type": "journal-article",
"update-policy": "https://doi.org/10.3389/crossmark-policy",
"volume": "17"
}
