{"doi":"10.1016/j.xkme.2021.02.012","title":"Molecular Analysis of the Kidney From a Patient With COVID-19–Associated Collapsing Glomerulopathy","abstract":"Recent case reports suggest that coronavirus disease 2019 (COVID-19) is associated with collapsing glomerulopathy in African Americans with apolipoprotein L1 gene (APOL1) risk alleles; however, it is unclear whether disease pathogenesis is similar to HIV-associated nephropathy. RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19–associated collapsing glomerulopathy and APOL1 risk alleles (G1/G1) revealed similar levels of APOL1 and angiotensin-converting enzyme 2 (ACE2) messenger RNA transcripts as compared with 12 control kidney samples downloaded from the GTEx (Genotype-Tissue Expression) Portal. Whole-genome sequencing of the COVID-19–associated collapsing glomerulopathy kidney sample identified 4 indel gene variants, 3 of which are of unknown significance with respect to chronic kidney disease and/or focal segmental glomerulosclerosis. Molecular profiling of the kidney demonstrated activation of COVID-19–associated cell injury pathways such as inflammation and coagulation. Evidence for direct severe acute respiratory syndrome coronavirus 2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 (signal transducer and activator of transcription 3) in both COVID-19–associated collapsing glomerulopathy and HIV-associated nephropathy as compared with control kidney tissue. Importantly, interleukin 6–induced activation of STAT3 may be a targetable mechanism driving COVID-19–associated acute kidney injury. Recent case reports suggest that coronavirus disease 2019 (COVID-19) is associated with collapsing glomerulopathy in African Americans with apolipoprotein L1 gene (APOL1) risk alleles; however, it is unclear whether disease pathogenesis is similar to HIV-associated nephropathy. RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19–associated collapsing glomerulopathy and APOL1 risk alleles (G1/G1) revealed similar levels of APOL1 and angiotensin-converting enzyme 2 (ACE2) messenger RNA transcripts as compared with 12 control kidney samples downloaded from the GTEx (Genotype-Tissue Expression) Portal. Whole-genome sequencing of the COVID-19–associated collapsing glomerulopathy kidney sample identified 4 indel gene variants, 3 of which are of unknown significance with respect to chronic kidney disease and/or focal segmental glomerulosclerosis. Molecular profiling of the kidney demonstrated activation of COVID-19–associated cell injury pathways such as inflammation and coagulation. Evidence for direct severe acute respiratory syndrome coronavirus 2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 (signal transducer and activator of transcription 3) in both COVID-19–associated collapsing glomerulopathy and HIV-associated nephropathy as compared with control kidney tissue. Importantly, interleukin 6–induced activation of STAT3 may be a targetable mechanism driving COVID-19–associated acute kidney injury.","journal":"Kidney Medicine","year":2021,"id":167853,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":696199,"name":"Xuezhu Li","orcid":null,"position":1,"is_corresponding":false},{"id":439527,"name":"Fadi Salem","orcid":"0000-0002-2603-2778","position":2,"is_corresponding":false},{"id":386583,"name":"Zhengzi Yi","orcid":null,"position":3,"is_corresponding":false},{"id":469753,"name":"Zeguo Sun","orcid":"0000-0001-5542-2284","position":4,"is_corresponding":false},{"id":241216,"name":"Lili Chan","orcid":"0000-0003-4300-5760","position":5,"is_corresponding":false},{"id":696200,"name":"Miriam Chung","orcid":null,"position":6,"is_corresponding":false},{"id":695687,"name":"Jorge Rodriguez","orcid":"0000-0002-7891-5863","position":7,"is_corresponding":false},{"id":58024,"name":"Ha My T. Vy","orcid":"0000-0002-5117-3740","position":8,"is_corresponding":false},{"id":5026,"name":"Girish N. Nadkarni","orcid":"0000-0001-6319-4314","position":9,"is_corresponding":false},{"id":81451,"name":"Jenny Wong","orcid":null,"position":10,"is_corresponding":false},{"id":289961,"name":"Jia Fu","orcid":"0000-0002-8280-3813","position":11,"is_corresponding":false},{"id":289963,"name":"Kyung Lee","orcid":"0000-0002-9756-1765","position":12,"is_corresponding":false},{"id":301627,"name":"Weijia Zhang","orcid":"0000-0001-6928-0416","position":13,"is_corresponding":false},{"id":263575,"name":"John Cijiang He","orcid":"0000-0002-1502-2849","position":14,"is_corresponding":false},{"id":263576,"name":"Kirk N. 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