{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:34:48Z","timestamp":1792604088659,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>According to data from large national registries, almost 20%\u201325% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>ES was proposed in routine practice for patients with UKD including kidney biopsy from January 2019 to December 2021. Mutations were detected using a targeted bioinformatic customized kidney gene panel (675 genes). The pathogenicity was assessed using American College of Medical Genetics guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included 230 adult patients, median age 47.5 years. Consanguinity was reported by 25 patients. A family history of kidney disease was documented in 115 patients (50%). Kidney biopsies were either inconclusive in 69 patients (30.1%) or impossible in 71 (30.9%). We detected 28 monogenic renal disorders in 75 (32.6%) patients. Collagenopathies was the most common genetic kidney diagnosis (46.7%), with COL4A3 and COL4A4 accounting for 80% of these diagnoses. Tubulopathies (16%) and ciliopathies (14.7%) yielded, respectively, the second and third genetic kidney diagnosis category and UMOD-associated nephropathy as the main genetic findings for tubulopathies (7\/11). Ten of the 22 patients having ES \u201cfirst\u201d eventually received a positive diagnosis, thereby avoiding 11 biopsies. Among the 44 patients with glomerular, tubulo-interstitial or vascular nephropathy, 13 (29.5%) were phenocopies. The diagnostic yield of ES was higher in female patients (P\u00a0=\u00a0.02) and in patients with a family history of kidney disease (P\u00a0&amp;lt;\u00a0.0001), reaching 56.8% when the patient had both first- and second-degree family history of renal disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Genetic diagnosis has provided new clinical insights by clarifying or reclassifying kidney disease etiology in over a third of UKD patients. Exome \u201cfirst\u201d may have a significant positive diagnostic yield, thus avoiding invasive kidney biopsy; moreover, the diagnostic yield remains elevated even when biopsy is impossible or inconclusive. ES provides a clinical benefit for routine nephrological healthcare in patients with UKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfad099","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T11:21:33Z","timestamp":1682508093000},"source":"Crossref","is-referenced-by-count":20,"title":["Beyond the kidney biopsy: genomic approach to undetermined kidney diseases"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-0913","authenticated-orcid":false,"given":"Thomas","family":"Robert","sequence":"first","affiliation":[{"name":"Centre of Nephrology and Renal Transplantation, H\u00f4pital de la Conception, CHU de Marseille , Marseille , France"},{"name":"Marseille Medical Genetics, Bioinformatics & Genetics, INSERM U1251, Aix-Marseille Universit\u00e9 , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Raymond","sequence":"additional","affiliation":[{"name":"Genetics Department, Laboratoire Eurofins Biomnis , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Dancer","sequence":"additional","affiliation":[{"name":"Genetics Department, Laboratoire Eurofins Biomnis , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Torrents","sequence":"additional","affiliation":[{"name":"Department of Renal Pathology, CHU Timone, AP-HM , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Jourde-Chiche","sequence":"additional","affiliation":[{"name":"Centre of Nephrology and Renal Transplantation, H\u00f4pital de la Conception, CHU de Marseille , Marseille , France"},{"name":"Aix-Marseille Univ, INSERM, INRAE, C2VN , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Burtey","sequence":"additional","affiliation":[{"name":"Centre of Nephrology and Renal Transplantation, H\u00f4pital de la Conception, CHU de Marseille , Marseille , France"},{"name":"Aix-Marseille Univ, INSERM, INRAE, C2VN , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"B\u00e9roud","sequence":"additional","affiliation":[{"name":"Marseille Medical Genetics, Bioinformatics & Genetics, INSERM U1251, Aix-Marseille Universit\u00e9 , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Mesnard","sequence":"additional","affiliation":[{"name":"Urgences N\u00e9phrologiques et Transplantation R\u00e9nale, Sorbonne Universit\u00e9, APHP, H\u00f4pital Tenon , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"2024020711372639700_bib1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/ndt\/gfu294","article-title":"Disease burden and risk profile in referred patients with moderate chronic kidney disease: composition of the German Chronic Kidney Disease (GCKD) cohort","volume":"30","author":"Titze","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"2024020711372639700_bib2","doi-asserted-by":"crossref","first-page":"A7","DOI":"10.1053\/j.ajkd.2021.01.002","article-title":"US Renal Data System 2020 Annual Data Report: epidemiology of kidney disease in the United States","volume":"77","author":"Johansen","year":"2021","journal-title":"Am J Kidney Dis"},{"key":"2024020711372639700_bib3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.kint.2018.10.031","article-title":"Monogenic causes of chronic kidney disease in adults","volume":"95","author":"Connaughton","year":"2019","journal-title":"Kidney Int"},{"key":"2024020711372639700_bib4","doi-asserted-by":"crossref","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":"2024020711372639700_bib5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.kint.2019.01.038","article-title":"Value of renal gene panel diagnostics in adults waiting for kidney transplantation due to undetermined end-stage renal disease","volume":"96","author":"Ottlewski","year":"2019","journal-title":"Kidney Int"},{"key":"2024020711372639700_bib6","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1136\/jmg-2022-108439","article-title":"Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases","volume":"59","author":"Testard","year":"2022","journal-title":"J Med Genet"},{"key":"2024020711372639700_bib7","doi-asserted-by":"crossref","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":"2024020711372639700_bib8","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1681\/ASN.2011040388","article-title":"APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy","volume":"22","author":"Kopp","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"2024020711372639700_bib9","doi-asserted-by":"crossref","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":"2024020711372639700_bib10","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2215\/CJN.08750718","article-title":"Integration of genetic testing and pathology for the diagnosis of adults with FSGS","volume":"14","author":"Yao","year":"2019","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024020711372639700_bib11","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1681\/ASN.2017121265","article-title":"Whole-exome sequencing identifies causative mutations in families with congenital anomalies of the kidney and urinary tract","volume":"29","author":"van der Ven","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"2024020711372639700_bib12","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/ndt\/gfab019","article-title":"Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players","volume":"37","author":"Domingo-Gallego","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2024020711372639700_bib13","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.kint.2018.02.027","article-title":"A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases","volume":"94","author":"Bullich","year":"2018","journal-title":"Kidney Int"},{"key":"2024020711372639700_bib14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1681\/ASN.2018060575","article-title":"Whole-exome sequencing enables a precision medicine approach for kidney transplant recipients","volume":"30","author":"Mann","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"2024020711372639700_bib15","doi-asserted-by":"crossref","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global Prevalence of chronic kidney disease - a systematic review and meta-analysis","volume":"11","author":"Hill","year":"2016","journal-title":"PLoS One"},{"key":"2024020711372639700_bib16","doi-asserted-by":"crossref","first-page":"12117","DOI":"10.1073\/pnas.94.22.12117","article-title":"Gene-based approach to human gene-phenotype correlations","volume":"94","author":"Dryja","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020711372639700_bib17","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1399-3046.2007.00704.x","article-title":"Contributions of the transplant registry: the 2006 annual report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)","volume":"11","author":"Smith","year":"2007","journal-title":"Pediatr Transplant"},{"key":"2024020711372639700_bib18","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.2215\/CJN.19171220","article-title":"Genetic basis of type IV collagen disorders of the kidney","volume":"16","author":"Quinlan","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024020711372639700_bib19","doi-asserted-by":"crossref","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":"2024020711372639700_bib20","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/ng.377","article-title":"Multiple loci associated with indices of renal function and chronic kidney disease","volume":"41","author":"K\u00f6ttgen","year":"2009","journal-title":"Nat Genet"},{"key":"2024020711372639700_bib21","doi-asserted-by":"crossref","first-page":"e2114734119","DOI":"10.1073\/pnas.2114734119","article-title":"An intermediate-effect size variant in","volume":"119","author":"Olinger","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020711372639700_bib22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12882-018-1107-y","article-title":"Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease","volume":"19","author":"Gast","year":"2018","journal-title":"BMC Nephrol"},{"key":"2024020711372639700_bib23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1053\/j.ajkd.2020.07.003","article-title":"Phenocopies, phenotypic expansion, and coincidental diagnoses: time to abandon targeted gene panels?","volume":"76","author":"Ahram","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"2024020711372639700_bib24","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41436-021-01127-8","article-title":"The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation","volume":"23","author":"Schrezenmeier","year":"2021","journal-title":"Genet Med"},{"key":"2024020711372639700_bib25","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1093\/ndt\/gfac319","article-title":"Exome sequencing reanalysis solved case in undetermined","volume":"38","author":"Robert","year":"2023","journal-title":"Nephrol Dial Transplant"},{"key":"2024020711372639700_bib26","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ajhg.2022.03.015","article-title":"Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations","volume":"109","author":"Devane","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2024020711372639700_bib27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2215\/CJN.15161219","article-title":"APOL1 nephropathy: from genetics to clinical applications","volume":"16","author":"Friedman","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024020711372639700_bib28","doi-asserted-by":"crossref","first-page":"205435811878936","DOI":"10.1177\/2054358118789368","article-title":"Opportunities and challenges for genetic studies of end-stage renal disease in Canada","volume":"5","author":"Kalatharan","year":"2018","journal-title":"Can J Kidney Health Dis"},{"key":"2024020711372639700_bib29","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.kint.2022.03.019","article-title":"Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference","volume":"101","year":"2022","journal-title":"Kidney Int"},{"key":"2024020711372639700_bib30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1053\/j.ajkd.2019.12.008","article-title":"Exome sequencing and identification of phenocopies in patients with clinically presumed hereditary nephropathies","volume":"76","author":"Riedhammer","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"2024020711372639700_bib31","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/ki.2015.28","article-title":"Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management\u2014A KDIGO consensus report","volume":"88","author":"Eckardt","year":"2015","journal-title":"Kidney Int"},{"key":"2024020711372639700_bib32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41746-021-00428-1","article-title":"Medical records-based chronic kidney disease phenotype for clinical care and \u201cbig data\u201d observational and genetic studies","volume":"4","author":"Shang","year":"2021","journal-title":"NPJ Digit Med"},{"key":"2024020711372639700_bib33","doi-asserted-by":"crossref","first-page":"e113353","DOI":"10.1371\/journal.pone.0113353","article-title":"Familial risks of kidney failure in Sweden: a nationwide family study","volume":"9","author":"Akrawi","year":"2014","journal-title":"PLoS One"},{"key":"2024020711372639700_bib34","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.2215\/CJN.01680214","article-title":"et al. Familial clustering of ESRD in the Norwegian population","volume":"9","author":"Skrunes","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024020711372639700_bib35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrneph.2014.181","article-title":"Risk factors: familial aggregation of ESRD in Europeans-is it in the genes?","volume":"10","author":"Freedman","year":"2014","journal-title":"Nat Rev Nephrol"},{"key":"2024020711372639700_bib36","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000436983","article-title":"The Irish kidney gene project\u2014prevalence of family history in patients with kidney disease in Ireland","volume":"130","author":"Connaughton","year":"2015","journal-title":"Nephron"},{"key":"2024020711372639700_bib37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.semnephrol.2022.04.002","article-title":"X-linked kidney disorders in women","volume":"42","author":"Quinlan","year":"2022","journal-title":"Semin Nephrol"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfad099\/50518137\/sfad099.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/17\/1\/sfad099\/56610610\/sfad099.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/17\/1\/sfad099\/56610610\/sfad099.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T11:38:38Z","timestamp":1707305918000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfad099\/7143127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfad099","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2023,4,25]]},"article-number":"sfad099"}}