{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:26:38Z","timestamp":1783121198305,"version":"3.54.6"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alport syndromes (AS) are the second leading genetic cause of kidney failure. Whether the multiple kidney cysts (MKC) phenotype belongs to the AS spectrum remains debated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This multicenter retrospective study focused on patients genotyped with pathogenic COL4A3, COL4A4, or COL4A5 variants (classified as ACMG-AMP 4 or 5) between January 2011 and January 2023 across four French university hospitals. The study aimed to compare characteristics between two groups based on the presence or absence of MKC, defined by three or more cysts per kidney. The MKC group was compared to a control group with negative exome sequencing results for undetermined kidney disease (ES-UKD) to assess the association between MKC and AS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among the 257 AS patients included, 38 (14.8%) presented MKC without variation from hereditary cystic kidney panel. MKC showed a significant association with male gender (P\u00a0=\u00a00.004), cardiovascular risk factors, and loss of function variants (P\u00a0=\u00a00.012). Kidney failure onset appeared significantly later, by 6 years, in MKC patients (P\u00a0=\u00a00.035). Comparison with the ES-UKD (n\u00a0=\u00a0990) control group showed no significant association between AS and MKC by univariate and multivariate analysis. Multivariate analysis identified patient age and male gender (P\u00a0&amp;lt;\u00a00.001) as factors linked to MKC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A 14.8% prevalence of MKC was found in our cohort of 257 patients with AS. MKC-AS patients exhibited clinical and histological characteristics akin to nephroangiosclerosis. Our comprehensive analysis, incorporating a sizable ES-UKD cohort, revealed no significant association between MKC and AS, thus questioning the inclusion of MKC within the spectrum of AS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfae290","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T02:51:57Z","timestamp":1734576717000},"page":"1408-1415","source":"Crossref","is-referenced-by-count":6,"title":["Challenging the narrative of Alport syndrome spectrum: no link with cystic phenotype"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9830-640X","authenticated-orcid":false,"given":"Marie-Sophie","family":"Pagniez","sequence":"first","affiliation":[{"name":"CHU Lille, University of Lille Department of Nephrology, Kidney Transplantation and Dialysis, , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9031-1862","authenticated-orcid":false,"given":"Yannis","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Tenon Hospital Service de Soins Intensifs N\u00e9phrologiques et Rein Aigu (SINRA), French Intensive Renal Network, , Assistance Publique-H\u00f4pitaux de Paris, Paris ,","place":["France"]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Sorbonne Universit\u00e9, , Unit\u00e9 Mixte de Recherche 1155, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Fages","sequence":"additional","affiliation":[{"name":"CHU Lille, University of Lille Department of Nephrology, Kidney Transplantation and Dialysis, , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Larrue","sequence":"additional","affiliation":[{"name":"University of Lille Department of Toxicology and Genopathies, CHU Lille, , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoth\u00e9e","family":"Laboux","sequence":"additional","affiliation":[{"name":"CHU Lille, University of Lille Department of Nephrology, Kidney Transplantation and Dialysis, , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Gatinois","sequence":"additional","affiliation":[{"name":"Dialysis and Apheresis, CHU Bordeaux Department of Nephrology, Transplantation, , Bordeaux ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Letavernier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Sorbonne Universit\u00e9, , Unit\u00e9 Mixte de Recherche 1155, Paris ,","place":["France"]},{"name":"Tenon Hospital Service d'Explorations Fonctionnelles et Multidisciplinaire (EFM), , Assistance Publique-H\u00f4pitaux de Paris, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Rigothier","sequence":"additional","affiliation":[{"name":"Dialysis and Apheresis, CHU Bordeaux Department of Nephrology, Transplantation, , Bordeaux ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Glowacki","sequence":"additional","affiliation":[{"name":"CHU Lille, University of Lille Department of Nephrology, Kidney Transplantation and Dialysis, , Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-3757","authenticated-orcid":false,"given":"Laurent","family":"Mesnard","sequence":"additional","affiliation":[{"name":"Tenon Hospital Service de Soins Intensifs N\u00e9phrologiques et Rein Aigu (SINRA), French Intensive Renal Network, , Assistance Publique-H\u00f4pitaux de Paris, Paris ,","place":["France"]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Sorbonne Universit\u00e9, , Unit\u00e9 Mixte de Recherche 1155, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-0913","authenticated-orcid":false,"given":"Thomas","family":"Robert","sequence":"additional","affiliation":[{"name":"La Conception Hospital Centre de N\u00e9phrologie et transplantation r\u00e9nale, Assistance publique-H\u00f4pitaux de Marseille, , Marseille ,","place":["France"]},{"name":"Aix Marseille Universit\u00e9 , INSERM, INRAE, C2VN, Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"2025063007561413700_bib1","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1681\/ASN.2020071065","article-title":"Prevalence estimates of predicted pathogenic COL4A3\u2013COL4A5 variants in a population sequencing database and their implications for alport syndrome","volume":"32","author":"Gibson","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"2025063007561413700_bib2","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.kint.2017.12.018","article-title":"Alport syndrome: a unified classification of genetic disorders of collagen IV \u03b1345: a position paper of the Alport Syndrome Classification Working Group","volume":"93","author":"Kashtan","year":"2018","journal-title":"Kidney Int"},{"key":"2025063007561413700_bib3","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.xkme.2020.05.014","article-title":"Alport Syndrome classification and management","volume":"2","author":"Warady","year":"2020","journal-title":"Kidney Med"},{"key":"2025063007561413700_bib4","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1056\/NEJMoa1806891","article-title":"Diagnostic utility of exome sequencing for kidney disease","volume":"380","author":"Groopman","year":"2019","journal-title":"N Engl J Med"},{"key":"2025063007561413700_bib5","doi-asserted-by":"publisher","first-page":"sfad099","DOI":"10.1093\/ckj\/sfad099","article-title":"Beyond the kidney biopsy: genomic approach to undetermined kidney diseases","volume":"17","author":"Robert","year":"2024","journal-title":"Clin Kidney J"},{"key":"2025063007561413700_bib6","doi-asserted-by":"publisher","first-page":"865034","DOI":"10.3389\/fmed.2022.865034","article-title":"Genotype\u2013phenotype correlations for pathogenic COL4A3\u2013COL4A5 variants in X-linked, autosomal recessive, and autosomal dominant alport syndrome","volume":"9","author":"Savige","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"2025063007561413700_bib7","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1053\/j.ajkd.2021.02.326","article-title":"Clinical and genetic features of autosomal dominant Alport syndrome: a cohort study","volume":"78","author":"Furlano","year":"2021","journal-title":"Am J Kidney Dis"},{"key":"2025063007561413700_bib8","doi-asserted-by":"publisher","first-page":"703","DOI":"10.2215\/CJN.10581014","article-title":"Ocular features in Alport syndrome: pathogenesis and clinical significance","volume":"10","author":"Savige","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025063007561413700_bib9","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1681\/ASN.2009070784","article-title":"Genotype\u2013phenotype correlation in X-linked Alport syndrome","volume":"21","author":"Bekheirnia","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"2025063007561413700_bib10","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1053\/j.ajkd.2021.04.017","article-title":"Pathogenic variants in the genes affected in Alport syndrome (COL4A3\u2013COL4A5) and their association with other kidney conditions: a review","volume":"78","author":"Savige","year":"2021","journal-title":"Am J Kidney Dis"},{"key":"2025063007561413700_bib11","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1093\/ndt\/gfp158","article-title":"Clinico-pathological correlations in 127 patients in 11 large pedigrees, segregating one of three heterozygous mutations in the COL4A3\/COL4A4 genes associated with familial haematuria and significant late progression to proteinuria and chronic kidney disease from focal segmental glomerulosclerosis","volume":"24","author":"Pierides","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"2025063007561413700_bib12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ekir.2019.09.004","article-title":"Collagen IV gene mutations in adults with bilateral renal cysts and CKD","volume":"5","author":"Gulati","year":"2020","journal-title":"Kidney Int Rep"},{"key":"2025063007561413700_bib13","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1056\/NEJMoa071906","article-title":"COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps","volume":"357","author":"Plaisier","year":"2007","journal-title":"N Engl J Med"},{"key":"2025063007561413700_bib14","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1681\/ASN.2014121217","article-title":"HANAC Syndrome Col4a1 mutation causes neonate glomerular hyperpermeability and adult glomerulocystic kidney disease","volume":"27","author":"Chen","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2025063007561413700_bib15","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/s41431-021-00858-1","article-title":"Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria","volume":"29","author":"Savige","year":"2021","journal-title":"Eur J Hum Genet"},{"key":"2025063007561413700_bib16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2215\/CJN.04230321","article-title":"Guidelines for genetic testing and management of Alport syndrome","volume":"17","author":"Savige","year":"2022","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025063007561413700_bib17","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1093\/ndt\/gfae002","article-title":"Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome","volume":"8","author":"Bada-Bosch","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2025063007561413700_bib18","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/ndt\/gfae031","article-title":"Increased prevalence of kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants","volume":"39","author":"Furlano","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2025063007561413700_bib19","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1053\/j.ajkd.2024.02.005","article-title":"Clinical significance of the cystic phenotype in Alport syndrome","volume":"84","author":"Zeni","year":"2024","journal-title":"Am J Kidney Dis"},{"key":"2025063007561413700_bib20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"2025063007561413700_bib21","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson","year":"2017","journal-title":"Hum Genet"},{"key":"2025063007561413700_bib22","article-title":"Cystic renal disease (Version 9.6) [Internet]"},{"key":"2025063007561413700_bib23","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/ckj\/sfu033","article-title":"Multiple kidney cysts in thin basement membrane disease with proteinuria and kidney function impairment","volume":"7","author":"Sevillano","year":"2014","journal-title":"Clin Kidney J"},{"key":"2025063007561413700_bib24","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ekir.2021.11.004","article-title":"Alport syndrome with kidney cysts is still Alport syndrome","volume":"7","author":"Savige","year":"2021","journal-title":"Kidney Int Rep"},{"key":"2025063007561413700_bib25","doi-asserted-by":"publisher","first-page":"8318","DOI":"10.1038\/s41467-023-43878-9","article-title":"Polygenic risk alters the penetrance of monogenic kidney disease","volume":"14","author":"Khan","year":"2023","journal-title":"Nat Commun"},{"key":"2025063007561413700_bib26"},{"key":"2025063007561413700_bib27","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41586-023-06957-x","article-title":"Genomic data in the All of Us Research Program","volume":"627","author":"All of Us Research Program Genomics Investigators","year":"2024","journal-title":"Nature"},{"key":"2025063007561413700_bib28","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1681\/ASN.2021111447","article-title":"Genetic variants of the COL4A3, COL4A4, and COL4A5 genes contribute to thinned glomerular basement membrane lesions in sporadic IgA nephropathy patients","volume":"34","author":"Yuan","year":"2023","journal-title":"J Am Soc Nephrol"},{"key":"2025063007561413700_bib29","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.ekir.2021.02.022","article-title":"Rare collagenous heterozygote variants in children with IgA nephropathy","volume":"6","author":"Cambier","year":"2021","journal-title":"Kidney Int Rep"},{"key":"2025063007561413700_bib30","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1007\/s00261-018-1565-5","article-title":"Prevalence of renal cysts and association with risk factors in a general population: an MRI-based study","volume":"43","author":"Mensel","year":"2018","journal-title":"Abdom Radiol (NY)"},{"key":"2025063007561413700_bib31","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.kint.2023.05.006","article-title":"A wave of deep intronic mutations in X-linked Alport Syndrome","volume":"104","author":"Boisson","year":"2023","journal-title":"Kidney Int"},{"key":"2025063007561413700_bib32","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/ki.1994.354","article-title":"Hereditary and acquired cystic disease of the kidney","volume":"46","author":"Fick","year":"1994","journal-title":"Kidney Int"},{"key":"2025063007561413700_bib33","first-page":"299","article-title":"Acquired renal cysts in uremic patients\u2014In vivo demonstration by computed tomography","volume":"14","author":"Bommer","year":"1980","journal-title":"Clin Nephrol"},{"key":"2025063007561413700_bib34","first-page":"373","article-title":"[Acquired renal cysts in patients on chronic hemodialysis treatment]","volume":"112","author":"Jaki\u0107","year":"1990","journal-title":"Lijec Vjesn"},{"key":"2025063007561413700_bib35","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1159\/000045562","article-title":"Incidence of acquired renal cysts in biopsy specimens","volume":"84","author":"Liu","year":"2000","journal-title":"Nephron"},{"key":"2025063007561413700_bib36","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1007\/s003300000601","article-title":"Acquired cystic kidney disease","volume":"10","author":"Choyke","year":"2000","journal-title":"Eur Radiol"},{"key":"2025063007561413700_bib37","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/00125480-200305000-00003","article-title":"Renal cystic neoplasms and renal neoplasms associated with cystic renal diseases: pathogenetic and molecular links","volume":"10","author":"Truong","year":"2003","journal-title":"Adv Anat Pathol"},{"key":"2025063007561413700_bib38","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/ki.1986.251","article-title":"Clinical characteristics and diagnostic considerations in acquired renal cystic disease","volume":"30","author":"Narasimhan","year":"1986","journal-title":"Kidney Int"},{"key":"2025063007561413700_bib39","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/ki.1991.192","article-title":"Acquired cystic kidney disease","volume":"40","author":"Grantham","year":"1991","journal-title":"Kidney Int"},{"key":"2025063007561413700_bib40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.matbio.2016.08.005","article-title":"Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome","volume":"57\u201158","author":"Cosgrove","year":"2017","journal-title":"Matrix Biol"},{"key":"2025063007561413700_bib41","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.ekir.2022.06.001","article-title":"Heterozygous pathogenic COL4A3 and COL4A4 variants (autosomal dominant Alport Syndrome) are common, and not typically associated with end-stage kidney failure, hearing loss, or ocular abnormalities","volume":"7","author":"Savige","year":"2022","journal-title":"Kidney Int Rep"},{"key":"2025063007561413700_bib42","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1093\/ndt\/17.11.1897","article-title":"Correlation of histopathological features and renal impairment in autosomal dominant Alport syndrome in bull terriers","volume":"17","author":"Hood","year":"2002","journal-title":"Nephrol Dial Transplant"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfae290\/61230937\/gfae290.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/7\/1408\/61230937\/gfae290.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/7\/1408\/61230937\/gfae290.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:56:20Z","timestamp":1751284580000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/40\/7\/1408\/7928132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,12,18]]},"published-print":{"date-parts":[[2025,6,30]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfae290","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2024,12,18]]}}}