{"doi":"10.1093/ndt/gfad058","title":"Oral antiviral therapies for COVID-19 in patients with advanced chronic kidney disease or kidney failure","abstract":"As of December 2022, over 651 million people have been diagnosed with coronavirus disease 2019 (COVID-19) and 6.6 million people have died of COVID-19 [1]. Chronic kidney disease (CKD) is an important independent risk factor for hospitalization and death due to COVID-19 [2, 3]. Although case fatality has decreased since the introduction of effective vaccines, patients with advanced CKD and kidney failure requiring kidney replacement therapy remain at high risk for severe COVID-19 outcomes; a recent report by Bell and colleagues found a 7% 30-day mortality risk after COVID-19 diagnosis in fully vaccinated patients with kidney failure [4]. Vaccine effectiveness may be attenuated in patients with kidney failure, and monoclonal therapies are no longer effective against current Omicron variants [5, 6]. Thus, there is a pressing need for effective antiviral therapies to decrease morbidity and mortality in this population. Nirmatrelvir/ritonavir and molnupiravir each received emergency use authorization (EUA) from the Food and Drug Administration in December 2021. Patients with advanced CKD [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2] and kidney failure were excluded from the trials that led to the approval of these agents [7, 8]. The EUA for molnupiravir includes all levels of eGFR because pharmacokinetic studies demonstrated that kidney impairment had a small impact on drug levels [8]; however, there are limited data on its use in advanced CKD and kidney failure. In contrast, a pharmacokinetic study of nirmatrelvir/ritonavir demonstrated significantly higher drug exposures in patients with impaired kidney function which led to the recommendation that the dose be reduced to 150/100 mg twice daily for patients with eGFR 30–59 mL/min/1.73 m2, and that nirmatrelvir/ritonavir be avoided in patients with eGFR <30 mL/min/1.73 m2 [9]. Because limited data exist on the use of either molnupiravir or nirmatrelvir/ritonavir in patients with eGFR <30 mL/min/1.73 m2, we sought to characterize real-world use within our healthcare network. In a large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire, we identified patients who were prescribed molnupiravir or nirmatrelvir/ritonavir between January and October 2022, during which Omicron and its subvariants have been the predominant strains in the USA [10]. We included those with eGFR <30 mL/min/1.73 m2 or kidney failure before beginning oral antiviral therapy. We defined baseline eGFR as the median of all eGFR measurements between 14 and 365 days prior to diagnosis of COVID-19 [11]. We reviewed all clinical documentation between the start date and 4 weeks after therapy completion to identify potential adverse events (AEs). This study was approved by the Mass General Brigham Institutional Review Board; the need for informed consent was waived. A total of 27 patients met the inclusion criteria; 15 received molnupiravir and 12 received dose-reduced nirmatrelvir/ritonavir. Baseline characteristics, comorbidities, concurrent monoclonal antibody use, vaccination status and type of COVID-19 diagnostic tests are shown in Table 1. Overall, the majority had pre-dialysis CKD, and more patients with kidney failure were prescribed molnupiravir (Table 1). All patients had previously received the primary series of COVID-19 vaccination prior to infection; the majority (77.7%) had received at least one booster. Diagnosis was confirmed in the outpatient setting in all cases, using an antigen test (N = 12, 44%) or reverse transcriptase polymerase chain reaction testing (N = 15, 56%). Fever and cough were the most common presenting symptoms (Table 1). Patient characteristics and adverse events. Among the patients with kidney failure, the three treated with molnupiravir included two receiving hemodialysis and one receiving peritoneal dialysis. The one patient with kidney failure who was treated with nirmatrelvir/ritonavir was receiving hemodialysis. aImmunos","journal":"Nephrology Dialysis Transplantation","year":2023,"id":365336,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991026,"name":"Destiny Harden","orcid":"0000-0003-3463-5429","position":1,"is_corresponding":false},{"id":991508,"name":"Daiana Moreno","orcid":null,"position":2,"is_corresponding":false},{"id":1120846,"name":"James E. Dinulos","orcid":"0000-0002-2725-9667","position":3,"is_corresponding":false},{"id":972784,"name":"Paul Hanna","orcid":"0000-0003-4976-9104","position":4,"is_corresponding":false},{"id":972783,"name":"Qiyu Wang","orcid":"0000-0003-4959-7437","position":5,"is_corresponding":false},{"id":379901,"name":"Arthur Y Kim","orcid":null,"position":6,"is_corresponding":false},{"id":263649,"name":"Meghan E. Sise","orcid":"0000-0002-4327-9713","position":7,"is_corresponding":false},{"id":473792,"name":"Wonkyung Cho","orcid":"0000-0002-0290-8667","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"36948600","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}