{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:56:55Z","timestamp":1792807015014,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,6]]},"abstract":"\n Background<\/jats:bold>\n The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-\/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear.\n <\/jats:p>\n \n Methods<\/jats:bold>\n We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (\n kl\/kl<\/jats:italic>\n ), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD.\n <\/jats:p>\n \n Results<\/jats:bold>\n In cultured VSMCs, treatment with zinc sulfate (ZnSO\n 4<\/jats:sub>\n ) blunted phosphate-induced calcification, osteo-\/chondrogenic signaling, and NF-\n \u03ba<\/jats:italic>\n B activation. ZnSO\n 4<\/jats:sub>\n increased the abundance of zinc-finger protein TNF-\n \u03b1<\/jats:italic>\n \u2013induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-\n \u03ba<\/jats:italic>\n B pathway, by zinc-sensing receptor ZnR\/GPR39-dependent upregulation of\n TNFAIP3<\/jats:italic>\n gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO\n 4<\/jats:sub>\n under high phosphate conditions.\n kl\/kl<\/jats:italic>\n mice showed reduced plasma zinc levels, and ZnSO\n 4<\/jats:sub>\n supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO\n 4<\/jats:sub>\n ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO\n 4<\/jats:sub>\n ameliorated the osteoinductive effects of uremic serum in VSMCs.\n <\/jats:p>\n \n Conclusions<\/jats:bold>\n Zinc supplementation ameliorates phosphate-induced osteo-\/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-\n \u03ba<\/jats:italic>\n B pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.\n <\/jats:p>","DOI":"10.1681\/asn.2017050492","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T10:30:20Z","timestamp":1523615420000},"page":"1636-1648","source":"Crossref","is-referenced-by-count":168,"title":["Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-\u03baB"],"prefix":"10.1681","volume":"29","author":[{"given":"Jakob","family":"Voelkl","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashad","family":"Tuffaha","sequence":"additional","affiliation":[{"name":"Department of Physiology I, Eberhard-Karls University, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang T.D.","family":"Luong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zickler","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaber","family":"Masyout","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Feger","sequence":"additional","affiliation":[{"name":"Department of Physiology I, Eberhard-Karls University, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Graz, Graz, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Blaschke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuro-o","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Jichi Medical University, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Tomaschitz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Graz, Graz, Austria;"},{"name":"Division of Internal Medicine, Specialist Clinic of Rehabilitation Bad Gleichenberg, Bad Gleichenberg, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Pilz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pasch","sequence":"additional","affiliation":[{"name":"Calciscon AG, Nidau-Biel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Uwe","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen E.","family":"Scherberich","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Clinical Immunology, Klinikum M\u00fcnchen-Harlaching, Teaching Hospital of the Ludwig-Maximilians-Universit\u00e4t, M\u00fcnchen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-1540","authenticated-orcid":false,"given":"Florian","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Physiology I, Eberhard-Karls University, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"},{"name":"Berlin Institute of Health (BIH), Berlin, Germany; and"},{"name":"Department of Internal Medicine and Cardiology, German Heart Center Berlin (DHZB), Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Alesutan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany;"},{"name":"Berlin Institute of Health (BIH), Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,4,13]]},"reference":[{"key":"B1-20230829","doi-asserted-by":"crossref","first-page":"F891","DOI":"10.1152\/ajprenal.00163.2014","article-title":"A current understanding of vascular calcification in CKD.","volume":"307","author":"Paloian","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"B2-20230829","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1681\/ASN.2011121191","article-title":"Mechanistic insights into vascular calcification in CKD.","volume":"24","author":"Shroff","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B3-20230829","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s11255-016-1413-x","article-title":"Assessment of abdominal aortic calcification at different stages of chronic kidney disease.","volume":"48","author":"Biyik","year":"2016","journal-title":"Int Urol Nephrol"},{"key":"B4-20230829","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1681\/ASN.2007080854","article-title":"Mechanisms of vascular calcification in chronic kidney disease.","volume":"19","author":"Moe","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"B5-20230829","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1053\/ajkd.1998.v31.pm9531176","article-title":"Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study.","volume":"31","author":"Block","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"B6-20230829","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ahj.2008.05.016","article-title":"Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: The Atherosclerosis Risk in Communities (ARIC) Study.","volume":"156","author":"Foley","year":"2008","journal-title":"Am Heart J"},{"key":"B7-20230829","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1093\/ndt\/gft041","article-title":"Vascular calcification--is aldosterone a culprit?","volume":"28","author":"Lang","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"B8-20230829","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000368268","article-title":"Impact of aldosterone on osteoinductive signaling and vascular calcification.","volume":"128","author":"Lang","year":"2014","journal-title":"Nephron, Physiol"},{"key":"B9-20230829","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1159\/000368524","article-title":"Inhibition of phosphate-induced vascular smooth muscle cell osteo-\/chondrogenic signaling and calcification by bafilomycin A1 and methylamine.","volume":"40","author":"Alesutan","year":"2015","journal-title":"Kidney Blood Press Res"},{"key":"B10-20230829","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1097\/01.ASN.0000128955.83129.9C","article-title":"Phosphate-induced vascular calcification: Role of pyrophosphate and osteopontin.","volume":"15","author":"Lomashvili","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B11-20230829","article-title":"Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation [published online ahead of print Sep 26, 2016].","author":"Lin","journal-title":"Cardiovasc Res"},{"key":"B12-20230829","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/ki.2012.40","article-title":"Activation of nuclear factor-kappa B accelerates vascular calcification by inhibiting ankylosis protein homolog expression.","volume":"82","author":"Zhao","year":"2012","journal-title":"Kidney Int"},{"key":"B13-20230829","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1080\/07315724.1989.10720305","article-title":"Zinc in kidney disease.","volume":"8","author":"Mahajan","year":"1989","journal-title":"J Am Coll Nutr"},{"key":"B14-20230829","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1159\/000183501","article-title":"Is zinc status a problem in the dietary treatment of chronic renal failure?","volume":"40","author":"Gilli","year":"1985","journal-title":"Nephron"},{"key":"B15-20230829","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1741-7015-7-25","article-title":"Trace elements in hemodialysis patients: A systematic review and meta-analysis.","volume":"7","author":"Tonelli","year":"2009","journal-title":"BMC Med"},{"key":"B16-20230829","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/nu4070676","article-title":"Zinc and regulation of inflammatory cytokines: Implications for cardiometabolic disease.","volume":"4","author":"Foster","year":"2012","journal-title":"Nutrients"},{"key":"B17-20230829","doi-asserted-by":"crossref","first-page":"e90558","DOI":"10.1371\/journal.pone.0090558","article-title":"Dietary zinc is a key environmental modifier in the progression of IgA nephropathy.","volume":"9","author":"Maiguma","year":"2014","journal-title":"PLoS One"},{"key":"B18-20230829","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1017\/S0007114508084079","article-title":"Low serum zinc concentrations predict mortality in patients referred to coronary angiography.","volume":"101","author":"Pilz","year":"2009","journal-title":"Br J Nutr"},{"key":"B19-20230829","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/mnfr.201100776","article-title":"Suboptimal dietary zinc intake promotes vascular inflammation and atherogenesis in a mouse model of atherosclerosis.","volume":"56","author":"Beattie","year":"2012","journal-title":"Mol Nutr Food Res"},{"key":"B20-20230829","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.freeradbiomed.2006.11.024","article-title":"Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet.","volume":"42","author":"Jenner","year":"2007","journal-title":"Free Radic Biol Med"},{"key":"B21-20230829","doi-asserted-by":"crossref","first-page":"e0148536","DOI":"10.1371\/journal.pone.0148536","article-title":"Zinc prevents abdominal aortic aneurysm formation by induction of A20-mediated suppression of NF-\u03baB pathway.","volume":"11","author":"Yan","year":"2016","journal-title":"PLoS One"},{"key":"B22-20230829","doi-asserted-by":"crossref","first-page":"e80115","DOI":"10.1371\/journal.pone.0080115","article-title":"Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults.","volume":"8","author":"Jung","year":"2013","journal-title":"PLoS One"},{"key":"B23-20230829","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s12011-011-9103-0","article-title":"The correlation of serum trace elements and heavy metals with carotid artery atherosclerosis in maintenance hemodialysis patients.","volume":"144","author":"Ari","year":"2011","journal-title":"Biol Trace Elem Res"},{"key":"B24-20230829","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1093\/eurheartj\/ehu163","article-title":"Medial vascular calcification revisited: Review and perspectives.","volume":"35","author":"Lanzer","year":"2014","journal-title":"Eur Heart J"},{"key":"B25-20230829","doi-asserted-by":"crossref","first-page":"C210","DOI":"10.1152\/ajpcell.00229.2010","article-title":"Role of calcium-phosphate deposition in vascular smooth muscle cell calcification.","volume":"300","author":"Villa-Bellosta","year":"2011","journal-title":"Am J Physiol Cell Physiol"},{"key":"B26-20230829","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/HJH.0000000000001202","article-title":"Inhibition of osteo\/chondrogenic transformation of vascular smooth muscle cells by MgCl2 via calcium-sensing receptor.","volume":"35","author":"Alesutan","year":"2017","journal-title":"J Hypertens"},{"key":"B27-20230829","first-page":"812","article-title":"Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice.","volume":"123","author":"Voelkl","year":"2013","journal-title":"J Clin Invest"},{"key":"B28-20230829","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/cvr\/cvw062","article-title":"Augmentation of phosphate-induced osteo-\/chondrogenic transformation of vascular smooth muscle cells by homoarginine.","volume":"110","author":"Alesutan","year":"2016","journal-title":"Cardiovasc Res"},{"key":"B29-20230829","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1681\/ASN.2014030230","article-title":"NH4Cl treatment prevents tissue calcification in klotho deficiency.","volume":"26","author":"Leibrock","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B30-20230829","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.yjmcc.2016.04.009","article-title":"AMP-activated protein kinase \u03b11-sensitive activation of AP-1 in cardiomyocytes.","volume":"97","author":"Voelkl","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"B31-20230829","doi-asserted-by":"crossref","first-page":"e3011","DOI":"10.1097\/MD.0000000000003011","article-title":"Plasma uromodulin correlates with kidney function and identifies early stages in chronic kidney disease patients.","volume":"95","author":"Steubl","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"B32-20230829","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1681\/ASN.2012030240","article-title":"Nanoparticle-based test measures overall propensity for calcification in serum.","volume":"23","author":"Pasch","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B33-20230829","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.bbrc.2009.12.027","article-title":"Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction.","volume":"391","author":"Lee","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B34-20230829","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1161\/CIRCRESAHA.115.306341","article-title":"Transcription factor Runx2 promotes aortic fibrosis and stiffness in Type 2 diabetes mellitus.","volume":"117","author":"Raaz","year":"2015","journal-title":"Circ Res"},{"key":"B35-20230829","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/jbmr.2420","article-title":"Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.","volume":"30","author":"Sheen","year":"2015","journal-title":"J Bone Miner Res"},{"key":"B36-20230829","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1016\/j.bcp.2010.06.044","article-title":"Expression, biological activities and mechanisms of action of A20 (TNFAIP3).","volume":"80","author":"Verstrepen","year":"2010","journal-title":"Biochem Pharmacol"},{"key":"B37-20230829","doi-asserted-by":"crossref","first-page":"820","DOI":"10.4049\/jimmunol.1600334","article-title":"A20 ameliorates intracerebral hemorrhage-induced inflammatory injury by regulating TRAF6 polyubiquitination.","volume":"198","author":"Meng","year":"2017","journal-title":"J Immunol"},{"key":"B38-20230829","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1016\/j.febslet.2008.06.030","article-title":"Molecular mechanism of Zn2+ agonism in the extracellular domain of GPR39.","volume":"582","author":"Storjohann","year":"2008","journal-title":"FEBS Lett"},{"key":"B39-20230829","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1742-2094-11-122","article-title":"A20 deficiency causes spontaneous neuroinflammation in mice.","volume":"11","author":"Guedes","year":"2014","journal-title":"J Neuroinflammation"},{"key":"B40-20230829","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/ng.874","article-title":"A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis.","volume":"43","author":"Matmati","year":"2011","journal-title":"Nat Genet"},{"key":"B41-20230829","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/ndt\/gfr375","article-title":"The chemistry of thiosulfate and vascular calcification.","volume":"27","author":"O\u2019Neill","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"B42-20230829","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1080\/00365513.2016.1201852","article-title":"Variation of trace element concentrations in patients undergoing hemodialysis in the north of Spain.","volume":"76","author":"G\u00f3mez de O\u00f1a","year":"2016","journal-title":"Scand J Clin Lab Invest"},{"key":"B43-20230829","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1681\/ASN.2014070670","article-title":"Calcification propensity and survival among renal transplant recipients.","volume":"27","author":"Keyzer","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B44-20230829","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1681\/ASN.2013060635","article-title":"Serum calcification propensity predicts all-cause mortality in predialysis CKD.","volume":"25","author":"Smith","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B45-20230829","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2215\/CJN.04720416","article-title":"Blood calcification propensity, cardiovascular events, and survival in patients receiving hemodialysis in the EVOLVE trial.","volume":"12","author":"Pasch","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B46-20230829","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/tri.12595","article-title":"Living kidney donation does not adversely affect serum calcification propensity and markers of vascular stiffness.","volume":"28","author":"de Seigneux","year":"2015","journal-title":"Transpl Int"},{"key":"B47-20230829","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12011-013-9639-2","article-title":"Effects of zinc supplement on plasma homocysteine level in end-stage renal disease patients: A double-blind randomized clinical trial.","volume":"153","author":"Pakfetrat","year":"2013","journal-title":"Biol Trace Elem Res"},{"key":"B48-20230829","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1053\/j.jrn.2009.04.005","article-title":"Effects of zinc supplementation on serum zinc and C-reactive protein concentrations in hemodialysis patients.","volume":"19","author":"Rashidi","year":"2009","journal-title":"J Ren Nutr"},{"key":"B49-20230829","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12882-015-0042-4","article-title":"Trace element supplementation in hemodialysis patients: A randomized controlled trial.","volume":"16","author":"Tonelli","year":"2015","journal-title":"BMC Nephrol"},{"key":"B50-20230829","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1517\/13543784.2013.778971","article-title":"Therapeutic potential of serum and glucocorticoid inducible kinase inhibition.","volume":"22","author":"Lang","year":"2013","journal-title":"Expert Opin Investig Drugs"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201806000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:30:49Z","timestamp":1786131049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201806000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,13]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2017050492","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.733042924.793545477","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,13]]}}}