{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:49:09Z","timestamp":1786135749529,"version":"build-2736575974"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-12-BSV1-0031-01"],"award-info":[{"award-number":["ANR-12-BSV1-0031-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE14-0032"],"award-info":[{"award-number":["ANR-17-CE14-0032"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic hypomagnesemia is commonly due to diarrhea, alcoholism, and drugs. More rarely, it is caused by genetic defects in the effectors of renal magnesium reabsorption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In an adult patient with acquired severe hypomagnesemia, hypocalcemia, tubulointerstitial nephropathy, and rapidly progressing kidney injury, similarities between the patient\u2019s presentation and features of genetic disorders of renal magnesium transport prompted us to investigate whether the patient had an acquired autoimmune cause of renal magnesium wasting. To determine if the patient\u2019s condition might be explained by autoantibodies directed against claudin-16 or claudin-19, transmembrane paracellular proteins involved in renal magnesium absorption, we conducted experiments with claudin knockout mice and transfected mouse kidney cells expressing human claudin-16 or claudin-19. We also examined effects on renal magnesium handling in rats given intravenous injections of IgG purified from sera from the patient or controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Experiments with the knockout mice and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      transfected cells demonstrated that hypomagnesemia in the patient was causally linked to autoantibodies directed against claudin-16, which controls paracellular magnesium reabsorption in the thick ascending limb of Henle\u2019s loop. Intravenous injection of IgG purified from the patient\u2019s serum induced a marked urinary waste of magnesium in rats. Immunosuppressive treatment combining plasma exchange and rituximab was associated with improvement in the patient\u2019s GFR, but hypomagnesemia persisted. The patient was subsequently diagnosed with a renal carcinoma that expressed a high level of claudin-16 mRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pathogenic claudin-16 autoantibodies represent a novel autoimmune cause of specific renal tubular transport disturbances and tubulointerstitial nephropathy. Screening for autoantibodies targeting claudin-16, and potentially other magnesium transporters or channels in the kidney, may be warranted in patients with acquired unexplained hypomagnesemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2022010060","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T11:40:18Z","timestamp":1655811618000},"page":"1402-1410","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 Autoantibodies"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-2064","authenticated-orcid":false,"given":"Lucile","family":"Figueres","sequence":"first","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Nantes, France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Prot-Bertoye","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Department of Physiology, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Brideau","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"N\u00e9el","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Nantes, France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Griveau","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Cheval","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"Bignon","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Dejoie","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0618-6187","authenticated-orcid":false,"given":"Simon","family":"Ville","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Nantes, France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie, Nantes, France"},{"name":"Department of Nephrology, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kandel-Aznar","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Moreau","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Houillier","sequence":"additional","affiliation":[{"name":"Centre de recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Department of Physiology, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte, Paris, France"},{"name":"CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Fakhouri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,7]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00012.2014","article-title":"Magnesium in man: Implications for health and disease","volume":"95","author":"de Baaij","year":"2015","journal-title":"Physiol Rev"},{"key":"B2-20250823","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-physiol-021113-170336","article-title":"Mechanisms and regulation of renal magnesium transport","volume":"76","author":"Houillier","year":"2014","journal-title":"Annu Rev Physiol"},{"key":"B3-20250823","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.kint.2017.09.032","article-title":"Claudins: A tale of interactions in the thick ascending limb","volume":"93","author":"Olinger","year":"2018","journal-title":"Kidney Int"},{"key":"B4-20250823","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/MNH.0000000000000238","article-title":"Mechanisms and causes of hypomagnesemia","volume":"25","author":"Agus","year":"2016","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B5-20250823","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1681\/ASN.2008010098","article-title":"Molecular determinants of magnesium homeostasis: Insights from human disease","volume":"19","author":"Alexander","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"B6-20250823","doi-asserted-by":"crossref","first-page":"F1152","DOI":"10.1152\/ajprenal.00499.2009","article-title":"Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting","volume":"298","author":"Will","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"B7-20250823","doi-asserted-by":"crossref","first-page":"14241","DOI":"10.1073\/pnas.1203834109","article-title":"Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis","volume":"109","author":"Breiderhoff","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B8-20250823","doi-asserted-by":"crossref","first-page":"F207","DOI":"10.1152\/ajprenal.00579.2020","article-title":"Differential localization patterns of claudin 10, 16, and 19 in human, mouse, and rat renal tubular epithelia","volume":"321","author":"Prot-Bertoye","year":"2021","journal-title":"Am J Physiol Renal Physiol"},{"key":"B9-20250823","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1007\/s00424-003-1108-x","article-title":"Differentiated thick ascending limb (TAL) cultured cells derived from SV40 transgenic mice express functional apical NHE2 isoform: Effect of nitric oxide","volume":"446","author":"Bourgeois","year":"2003","journal-title":"Pflugers Arch"},{"key":"B10-20250823","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1007\/s00467-004-1593-y","article-title":"Kimura disease with advanced renal damage with anti-tubular basement membrane antibody","volume":"19","author":"Dixit","year":"2004","journal-title":"Pediatr Nephrol"},{"key":"B11-20250823","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1681\/ASN.2015030334","article-title":"Immune complex tubulointerstitial nephritis due to autoantibodies to the proximal tubule brush border","volume":"27","author":"Rosales","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B12-20250823","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1681\/ASN.2015101126","article-title":"Autoantibodies targeting a collecting duct-specific water channel in tubulointerstitial nephritis","volume":"27","author":"Landegren","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B13-20250823","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1093\/ndt\/gfm890","article-title":"Presence of autoantibodies against tubular and uveal cells in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome","volume":"23","author":"Abed","year":"2008","journal-title":"Nephrol Dial Transplant"},{"key":"B14-20250823","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1152\/physrev.00019.2012","article-title":"Claudins and the modulation of tight junction permeability","volume":"93","author":"G\u00fcnzel","year":"2013","journal-title":"Physiol Rev"},{"key":"B15-20250823","first-page":"619","article-title":"Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex","volume":"118","author":"Hou","year":"2008","journal-title":"J Clin Invest"},{"key":"B16-20250823","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1210\/jc.2006-0200","article-title":"Unusual clinical presentation and possible rescue of a novel claudin-16 mutation","volume":"91","author":"M\u00fcller","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B17-20250823","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1074\/jbc.M007727200","article-title":"Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits","volume":"276","author":"Quitterer","year":"2001","journal-title":"J Biol Chem"},{"key":"B18-20250823","first-page":"281","article-title":"Passively transferred anti-brush border antibodies induce injury of proximal tubules in the absence of complement","volume":"56","author":"Noble","year":"1984","journal-title":"Clin Exp Immunol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2022010060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:49:04Z","timestamp":1786132144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2022010060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2022010060","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"2022-01-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-22","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}