{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:59Z","timestamp":1786480319997,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"abstract":"\n Background:<\/jats:title>\n \n Alport syndrome is a hereditary nephropathy caused by pathogenic variants in the\n COL4A3, COL4A4<\/jats:italic>\n , or\n COL4A5<\/jats:italic>\n genes, encoding type IV collagen chains that are essential for glomerular basement membrane integrity. The missense pathogenic variant p.Gly407Arg in\n COL4A3<\/jats:italic>\n has been reported in Portuguese families, but detailed phenotypic characterization remains limited. This study aimed to describe the renal and extra-renal manifestations and identify predictors of renal outcomes in a cohort of patients carrying the\n COL4A3<\/jats:italic>\n p.Gly407Arg variant.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n We conducted a retrospective observational study including 62 patients from 25 families followed at a tertiary nephrology center in northern Portugal between 2007 and 2025 with genetically confirmed Autosomal Dominant Alport syndrome due to monoallelic\n COL4A3<\/jats:italic>\n p.Gly407Arg pathogenic variant. Demographic, clinical, laboratory, audiologic, and ophthalmologic data were analyzed. Renal events were defined as incident kidney failure, estimated Glomerular Filtration Rate (eGFR) <15 mL\/min\/1.73 m\n 2<\/jats:sup>\n , or eGFR \u226530% decline from baseline sustained over time\n .<\/jats:bold>\n Changes in eGFR over time were analyzed using a univariate linear mixed effects model.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n At diagnosis, 98% of patients presented with microscopic hematuria, and 53% had proteinuria (urinary protein-creatinine ratio (UPCR) 240mg\/g, IQR 9\u2013840). The mean eGFR was 94 \u00b1 32 mL\/min\/1.73m\n 2<\/jats:sup>\n . Mean follow-up time in the study (from the initiation of clinical observation until the occurrence of the event or the end of follow-up) was 4.72 years (IQR 2.43-8.43). During a median follow-up of 4.72 years, 16 patients (26%) developed renal events, with 5 (8%) initiating KRT at a mean age of 58 (range 45-66) years. The mean renal survival was 67 years (63-72). Proteinuria \u2265500mg\/g was significantly associated with faster eGFR decline (\n p<\/jats:italic>\n < 0.001) and a higher risk of renal events (imputed as a time-varying variable, HR 1.03, 95% CI 1.001\u20131.059,\n p<\/jats:italic>\n = 0.04). Hearing loss occurred in 34% of patients and ocular changes in 18% of the patients evaluated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Patients carrying monoallelic\n COL4A3<\/jats:italic>\n p.Gly407Arg pathogenic variant exhibit variable phenotypic expression, with proteinuria representing the strongest predictor of renal function decline.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001184","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:01:15Z","timestamp":1775232075000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Insights Into the COL4A3 p.Gly407Arg Variant in Alport Syndrome"],"prefix":"10.34067","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-5792","authenticated-orcid":false,"given":"Ana Marta","family":"Gomes","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Nefrologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR - Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Centro Acad\u00e9mico Cl\u00ednico Egas Moniz Health AllianceCampus Universit\u00e1rio Santiago, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5731","authenticated-orcid":false,"given":"Cl\u00e1udia Falc\u00e3o","family":"Reis","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR - Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, Centro de Gen\u00e9tica M\u00e9dica Jacinto Magalh\u00e3es, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, Porto, Portugal"},{"name":"European Rare Kidney Reference Center (ERKNet), Centro Hospitalar Universit\u00e1rio do Porto, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7999-5691","authenticated-orcid":false,"given":"Joana","family":"Dias","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Nefrologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-9058","authenticated-orcid":false,"given":"Pedro Moreira","family":"Martins","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oftamologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-9406","authenticated-orcid":false,"given":"Nuno","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Otorrinolaringologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1608-0028","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Pediatria, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-4502","authenticated-orcid":false,"given":"Vit\u00f3ria","family":"Faria","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Nefrologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-5889","authenticated-orcid":false,"given":"Jorge","family":"Malheiro","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism, Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-9584","authenticated-orcid":false,"given":"Carolina","family":"Lemos","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR - Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Lopes","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Nefrologia, Unidade Local de Sa\u00fade Gaia\/Espinho, Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3903-0170","authenticated-orcid":false,"given":"Idalina","family":"Beir\u00e3o","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR - Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"},{"name":"Servi\u00e7o Nefrologia, Centro Hospitalar Universit\u00e1rio do Porto, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, Porto, Portugal"},{"name":"European Rare Kidney Reference Center (ERKNet), Centro Hospitalar Universit\u00e1rio do Porto, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,4,3]]},"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:03:34Z","timestamp":1786478614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34067\/kid.0000001184","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2025-12-01","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}