{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:16:27Z","timestamp":1783336587615,"version":"3.54.6"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFA0104500"],"award-info":[{"award-number":["2017YFA0104500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0904100"],"award-info":[{"award-number":["2016YFC0904100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0904103"],"award-info":[{"award-number":["2016YFC0904103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key R&D Projects of Jiangsu Province","award":["BE2016747"],"award-info":[{"award-number":["BE2016747"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alport syndrome (AS) is an inherited type IV collagen\u2013related disorder with an irreversible tendency to progress to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by mutations in the COL4A5 gene. The aim of this study was to investigate the effects of underlying mutations on clinical manifestations and the response to therapy in XLAS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective cohort study of 187 Chinese male patients with XLAS confirmed by pathological examination and genetic analysis. The Kaplan\u2013Meier method and Cox proportional hazards model were used to assess the age and risk of progression to ESRD under different genotypes and treatment conditions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A strong relationship between transcript type and renal outcome was observed, with the median age of ESRD onset being 22 years for truncating mutations and 39 years for non-truncating mutations. The response of affected patients to renin\u2013angiotensin\u2013aldosterone system (RAAS) blockers was genotype-associated. This therapy delayed the onset of ESRD by 16 years in patients with non-truncating mutations and 3 years in patients with truncating mutations. The efficacy of RAAS blockers functioned in a time-dependent manner, with a 7% reduction in the risk of progression to ESRD per each 6-month increase in treatment duration [hazard ratio 0.93 (95% confidence interval 0.89\u20130.96); P &amp;lt; 0.001].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Clinical features and response to RAAS blockers were observed to be strongly correlated with the genotypes of male XLAS patients. Genotyping of COL4A5 gene mutations is essential and is a useful tool to assess the prognosis of AS patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfac002","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T12:13:17Z","timestamp":1641557597000},"page":"2487-2495","source":"Crossref","is-referenced-by-count":21,"title":["Dissecting the genotype-phenotype correlation of <i>COL4A5<\/i> gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome"],"prefix":"10.1093","volume":"37","author":[{"given":"Hongling","family":"Di","sequence":"first","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biosystems Homeostasis and Protection of the Ministry of Education, Life Sciences Institute, Zhejiang University , Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzhi","family":"Gao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghua","family":"Huang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Yu","sequence":"additional","affiliation":[{"name":"Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Affiliated Jinling Hospital, Medical School of Nanjing University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"2022112304493660600_bib1","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1093\/ndt\/gfl090","article-title":"Quantitative analysis of type IV collagen subchains in the glomerular basement membrane of patients with Alport syndrome with confocal microscopy","volume":"21","author":"Su","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"2022112304493660600_bib2","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\u201358","author":"Cosgrove","year":"2017","journal-title":"Matrix Biol"},{"key":"2022112304493660600_bib3","doi-asserted-by":"crossref","first-page":"8767","DOI":"10.1074\/jbc.273.15.8767","article-title":"Glomerular basement membrane. 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