{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:29:40Z","timestamp":1783344580853,"version":"3.54.6"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T00:00:00Z","timestamp":1559520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Romanian Academy of Medical Sciences and European Regional Development Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Low-density lipoprotein cholesterol (LDL-C) levels almost constantly increased in patients with nephrotic syndrome (NS). Protein convertase subtilisin\/kexin type 9 (PCSK9) [accelerates LDL-receptor (LDL-R) degradation] is overexpressed by liver cells in NS. Their levels, correlated inversely to LDL-R expression and directly to LDL-C, seem to play a central role in hypercholesterolaemia in NS. Hypersynthesis resulting from sterol regulatory element-binding protein dysfunction, hyperactivity induced by c-inhibitor of apoptosis protein expressed in response to stimulation by tumour necrosis factor-\u03b1 produced by damaged podocytes and hypo-clearance are the main possible mechanisms. Increased LDL-C may damage all kidney cell populations (podocytes, mesangial and tubular cells) in a similar manner. Intracellular cholesterol accumulation produces oxidative stress, foam cell formation and apoptosis, all favoured by local inflammation. The cumulative effect of cellular lesions is worsened proteinuria and kidney function loss. Accordingly, NS patients should be considered high risk and treated by lowering LDL-C. However, there is still not enough evidence determining whether lipid-lowering agents are helpful in managing dyslipidaemia in NS. Based on good efficacy and safety proved in the general population, therapeutic modulation of PCSK9 via antibody therapy might be a reasonable solution. This article explores the established and forthcoming evidence implicating PCSK9 in LDL-C dysregulation in NS.<\/jats:p>","DOI":"10.1093\/ndt\/gfz108","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T11:17:17Z","timestamp":1556191037000},"page":"1663-1674","source":"Crossref","is-referenced-by-count":20,"title":["Protein convertase subtilisin\/kexin type 9 biology in nephrotic syndrome: implications for use as therapy"],"prefix":"10.1093","volume":"35","author":[{"given":"Ruxandra Mihaela","family":"Busuioc","sequence":"first","affiliation":[{"name":"\u201cCarol Davila\u201d University of Medicine and Pharmacy, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Covic","sequence":"additional","affiliation":[{"name":"\u201cGr. T. Popa,\u201d University of Medicine and Pharmacy, Iasi, Romania"},{"name":"Nephrology Clinic, Dialysis and Renal Transplant Center - \u2018C.I. Parhon\u2019 University Hospital Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Kanbay","sequence":"additional","affiliation":[{"name":"Koc University School of Medicine, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Lodz, Poland"},{"name":"Polish Mother\u2019s Memorial Hospital Research Institute, Lodz, Poland"},{"name":"Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-1588","authenticated-orcid":false,"given":"Alexandru","family":"Burlacu","sequence":"additional","affiliation":[{"name":"\u201cGr. T. Popa,\u201d University of Medicine and Pharmacy, Iasi, Romania"},{"name":"Head of Department of Interventional Cardiology \u2013 Cardiovascular Diseases Institute Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Mircescu","sequence":"additional","affiliation":[{"name":"\u201cCarol Davila\u201d University of Medicine and Pharmacy, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"2020100618542119400_gfz108-B1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/ndt\/gfu077","article-title":"Nephrotic syndrome redux","volume":"30","author":"Glassock","year":"2015","journal-title":"Nephrol Dial 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