{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:53:00Z","timestamp":1793242380221,"version":"4.5.0"},"reference-count":115,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2020B008"],"award-info":[{"award-number":["2020B008"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Albumin is the most abundant protein in blood plasma and acts as a carrier for many circulating molecules. Hypoalbuminaemia, mostly caused by either renal or liver disease or malnutrition, can perturb vascular homeostasis and is involved in the development of multiple diseases. Here we review four functions of albumin and the consequences of hypoalbuminaemia on vascular homeostasis. (i) Albumin is the main determinant of plasma colloid osmotic pressure. Hypoalbuminaemia was therefore thought to be the main mechanism for oedema in nephrotic syndrome (NS), however, experimental studies showed that intrarenal mechanisms rather than hypoalbuminaemia determine formation and, in particular, maintenance of oedema. (ii) Albumin functions as an interface between lysophosphatidylcholine (LPC) and circulating factors (lipoproteins and erythrocytes) and the endothelium. Consequently, hypoalbuminaemia results in higher LPC levels in lipoproteins and erythrocyte membrane, thereby increasing atherosclerotic properties of low-density lipoprotein and blood viscosity, respectively. Furthermore, albumin dose-dependently restores LPC-induced inhibition of vasodilation. (iii) Hypoalbuminaemia impacts on vascular nitric oxide (NO) signalling by directly increasing NO production in endothelial cells, leading to reduced NO sensitivity of vascular smooth muscle cells. (iv) Lastly, albumin binds free fatty acids (FFAs). FFAs can induce vascular smooth muscle cell apoptosis, uncouple endothelial NO synthase and decrease endothelium-dependent vasodilation. Unbound FFAs can increase the formation of reactive oxygen species by mitochondrial uncoupling in multiple cell types and induce hypertriglyceridemia in NS. In conclusion, albumin acts as an interface in the circulation and hypoalbuminaemia impairs multiple aspects of vascular function that may underlie the association of hypoalbuminaemia with adverse outcomes. However, hypoalbuminaemia is not a key to oedema in NS. These insights have therapeutic implications.<\/jats:p>","DOI":"10.1093\/ckj\/sfab194","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T17:58:51Z","timestamp":1633111131000},"page":"624-634","source":"Crossref","is-referenced-by-count":62,"title":["Albumin is an interface between blood plasma and cell membrane, and not just a sponge"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7133-3046","authenticated-orcid":false,"given":"Jens","family":"van de Wouw","sequence":"first","affiliation":[{"name":"Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2565-242X","authenticated-orcid":false,"given":"Jaap A","family":"Joles","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"2022033100230212300_bib1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2147\/IJGM.S102819","article-title":"Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements","volume":"9","author":"Levitt","year":"2016","journal-title":"Int J Gen Med"},{"issue":"Suppl 1","key":"2022033100230212300_bib2","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.2215\/CJN.03090509","article-title":"Biochemistry and biomarkers of inflamed patients: why look, what to assess","volume":"4","author":"Kaysen","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022033100230212300_bib3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0378-1119(82)90188-3","article-title":"The human serum albumin gene: structure of a unique locus","volume":"19","author":"Hawkins","year":"1982","journal-title":"Gene"},{"key":"2022033100230212300_bib4","volume-title":"All about Albumin: Biochemistry, Genetics, and Medical Applications","author":"Peters","year":"2008"},{"key":"2022033100230212300_bib5","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/bs.pmbts.2019.01.006","article-title":"Glycated albumin level is significantly decreased in patients suffering nephrotic syndrome","volume":"162","author":"Wang","year":"2019","journal-title":"Prog Mol Biol Transl Sci"},{"key":"2022033100230212300_bib6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/chir.20709","article-title":"Ligand binding strategies of human serum albumin: how can the cargo be utilized?","volume":"22","author":"Varshney","year":"2010","journal-title":"Chirality"},{"key":"2022033100230212300_bib7","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1007\/s11739-012-0802-0","article-title":"Hypoalbuminemia","volume":"7","author":"Gatta","year":"2012","journal-title":"Intern Emerg Med"},{"key":"2022033100230212300_bib8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1053\/j.ackd.2011.06.001","article-title":"Glomerular proteinuria: a complex interplay between unique players","volume":"18","author":"Garg","year":"2011","journal-title":"Adv Chronic Kidney Dis"},{"key":"2022033100230212300_bib9","first-page":"479","article-title":"Mechanisms and consequences of proteinuria","volume":"54","author":"Kaysen","year":"1986","journal-title":"Lab Invest"},{"key":"2022033100230212300_bib10","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1113\/jphysiol.1896.sp000596","article-title":"On the absorption of fluids from the connective tissue spaces","volume":"19","author":"Starling","year":"1896","journal-title":"J Physiol"},{"key":"2022033100230212300_bib11","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1113\/jphysiol.2003.049379","article-title":"In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle","volume":"552","author":"Gyenge","year":"2003","journal-title":"J Physiol"},{"key":"2022033100230212300_bib12","first-page":"H1222","article-title":"Interstitial exclusion of albumin in rat tissues measured by a continuous infusion method","volume":"263","author":"Wiig","year":"1992","journal-title":"Am J Physiol"},{"key":"2022033100230212300_bib13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1159\/000168654","article-title":"Plasma volume regulation: defences against edema formation (with special emphasis on hypoproteinemia)","volume":"13","author":"Joles","year":"1993","journal-title":"Am J Nephrol"},{"key":"2022033100230212300_bib14","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1007\/s00125-010-1910-x","article-title":"Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus","volume":"53","author":"Broekhuizen","year":"2010","journal-title":"Diabetologia"},{"key":"2022033100230212300_bib15","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/ki.1985.179","article-title":"Preservation of blood volume during edema removal in nephrotic subjects","volume":"28","author":"Geers","year":"1985","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib16","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ki.1986.248","article-title":"The importance of plasma protein for blood volume and blood pressure homeostasis","volume":"30","author":"Koomans","year":"1986","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib17","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1038\/ki.1996.207","article-title":"Blood volume, colloid osmotic pressure and F-cell ratio in children with the nephrotic syndrome","volume":"49","author":"Vande Walle","year":"1996","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1159\/000183302","article-title":"Plasma and blood volumes in patients with the nephrotic syndrome","volume":"38","author":"Geers","year":"1984","journal-title":"Nephron"},{"key":"2022033100230212300_bib19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1681\/ASN.V102323","article-title":"Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease","volume":"10","author":"Vande Walle","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"2022033100230212300_bib20","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/ki.1984.176","article-title":"Functional relationships in the nephrotic syndrome","volume":"26","author":"Geers","year":"1984","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib21","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/ki.2012.180","article-title":"The pathophysiology of edema formation in the nephrotic syndrome","volume":"82","author":"Siddall","year":"2012","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib22","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(95)91210-X","article-title":"Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms","volume":"346","author":"Vande Walle","year":"1995","journal-title":"Lancet"},{"key":"2022033100230212300_bib23","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1159\/000183392","article-title":"Sodium retention in nephrotic syndrome is due to an intrarenal defect: evidence from steroid-induced remission","volume":"39","author":"Brown","year":"1985","journal-title":"Nephron"},{"key":"2022033100230212300_bib24","first-page":"F887","article-title":"Hypoproteinemia and recovery from edema in dogs","volume":"254","author":"Joles","year":"1988","journal-title":"Am J Physiol"},{"key":"2022033100230212300_bib25","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1159\/000183505","article-title":"Lowered protein content of tissue fluid in patients with the nephrotic syndrome: observations during disease and recovery","volume":"40","author":"Koomans","year":"1985","journal-title":"Nephron"},{"key":"2022033100230212300_bib26","first-page":"F23","article-title":"Colloid osmotic pressure in young analbuminemic rats","volume":"257","author":"Joles","year":"1989","journal-title":"Am J Physiol"},{"key":"2022033100230212300_bib27","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1079\/BJN19790086","article-title":"Pathogenesis of oedema in protein-energy malnutrition: the significance of plasma colloid osmotic pressure","volume":"42","author":"Fiorotto","year":"1979","journal-title":"Br J Nutr"},{"key":"2022033100230212300_bib28","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0022-4804(89)90129-7","article-title":"Effect of hypoproteinemia on blood volume recovery after moderate hemorrhage in conscious splenectomized dogs","volume":"47","author":"Joles","year":"1989","journal-title":"J Surg Res"},{"key":"2022033100230212300_bib29","first-page":"H284","article-title":"Effects of hypoproteinemia on fluid volumes and arterial pressure","volume":"245","author":"Manning","year":"1983","journal-title":"Am J Physiol"},{"key":"2022033100230212300_bib30","first-page":"F91","article-title":"Effects of hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume","volume":"252","author":"Manning","year":"1987","journal-title":"Am J Physiol"},{"key":"2022033100230212300_bib31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1172\/JCI110756","article-title":"Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome","volume":"71","author":"Ichikawa","year":"1983","journal-title":"J Clin Invest"},{"key":"2022033100230212300_bib32","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/BF01486843","article-title":"Analbuminemia","volume":"61","author":"Russi","year":"1983","journal-title":"Klin Wochenschr"},{"key":"2022033100230212300_bib33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1097\/MNH.0000000000000578","article-title":"Mechanisms of sodium retention in nephrotic syndrome","volume":"29","author":"Hinrichs","year":"2020","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2022033100230212300_bib34","doi-asserted-by":"crossref","first-page":"36586","DOI":"10.1074\/jbc.M805676200","article-title":"Plasmin activates epithelial Na+ channels by cleaving the gamma subunit","volume":"283","author":"Passero","year":"2008","journal-title":"J Biol Chem"},{"key":"2022033100230212300_bib35","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1681\/ASN.2008040364","article-title":"Plasmin in nephrotic urine activates the epithelial sodium channel","volume":"20","author":"Svenningsen","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2022033100230212300_bib36","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s00424-017-2014-y","article-title":"Physiology and pathophysiology of the plasminogen system in the kidney","volume":"469","author":"Svenningsen","year":"2017","journal-title":"Pflugers Arch"},{"key":"2022033100230212300_bib37","first-page":"118","article-title":"Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome","volume":"124","author":"Vaziri","year":"1994","journal-title":"J Lab Clin Med"},{"key":"2022033100230212300_bib38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000501059","article-title":"Association of urinary plasminogen-plasmin with edema and epithelial sodium channel activation in patients with nephrotic syndrome","volume":"50","author":"Chen","year":"2019","journal-title":"Am J Nephrol"},{"key":"2022033100230212300_bib39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.kint.2017.07.023","article-title":"Aprotinin prevents proteolytic epithelial sodium channel (ENaC) activation and volume retention in nephrotic syndrome","volume":"93","author":"Bohnert","year":"2018","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib40","doi-asserted-by":"crossref","first-page":"e13743","DOI":"10.14814\/phy2.13743","article-title":"Amiloride resolves resistant edema and hypertension in a patient with nephrotic syndrome; a case report","volume":"6","author":"Hinrichs","year":"2018","journal-title":"Physiol Rep"},{"key":"2022033100230212300_bib41","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1053\/j.ajkd.2016.08.027","article-title":"Diuretic resistance","volume":"69","author":"Hoorn","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"2022033100230212300_bib42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12882-018-0916-3","article-title":"Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report","volume":"19","author":"Yamaguchi","year":"2018","journal-title":"BMC Nephrol"},{"key":"2022033100230212300_bib43","doi-asserted-by":"crossref","first-page":"e13286","DOI":"10.1111\/apha.13286","article-title":"Urokinase-type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)-mediated sodium retention in experimental nephrotic syndrome","volume":"227","author":"Bohnert","year":"2019","journal-title":"Acta Physiol (Oxf)"},{"key":"2022033100230212300_bib44","doi-asserted-by":"crossref","first-page":"e13362","DOI":"10.1111\/apha.13362","article-title":"Urokinase-type plasminogen activator contributes to amiloride-sensitive sodium retention in nephrotic range glomerular proteinuria in mice","volume":"227","author":"Hinrichs","year":"2019","journal-title":"Acta Physiol (Oxf)"},{"key":"2022033100230212300_bib45","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3390\/ijms20051149","article-title":"An updated review of lysophosphatidylcholine metabolism in human diseases","volume":"20","author":"Law","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2022033100230212300_bib46","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1046\/j.1523-1755.1999.0550031005.x","article-title":"Hypoalbuminemia increases lysophosphatidylcholine in low-density lipoprotein of normocholesterolemic subjects","volume":"55","author":"Vuong","year":"1999","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib47","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.prostaglandins.2006.10.006","article-title":"Albumin inhibits cytotoxic activity of lysophosphatidylcholine by direct binding","volume":"83","author":"Kim","year":"2007","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"2022033100230212300_bib48","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1046\/j.1523-1755.1999.00685.x","article-title":"Oxidative stress mediates apoptosis induced by oxidized low-density lipoprotein and oxidized lipoprotein(a)","volume":"56","author":"Heermeier","year":"1999","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1055\/s-2000-13208","article-title":"The endothelium and lipoproteins: insights from recent cell biology and animal studies","volume":"26","author":"Rader","year":"2000","journal-title":"Semin Thromb Hemost"},{"key":"2022033100230212300_bib50","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1083\/jcb.120.4.1011","article-title":"Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro","volume":"120","author":"Murugesan","year":"1993","journal-title":"J Cell Biol"},{"key":"2022033100230212300_bib51","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1172\/JCI118728","article-title":"Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein","volume":"97","author":"Murugesan","year":"1996","journal-title":"J Clin Invest"},{"key":"2022033100230212300_bib52","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1161\/01.ATV.0000052673.77316.01","article-title":"Lysophosphatidylcholine inhibits endothelial cell migration by increasing intracellular calcium and activating calpain","volume":"23","author":"Chaudhuri","year":"2003","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2022033100230212300_bib53","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1046\/j.1523-1755.1999.07115.x","article-title":"Endothelial function in proteinuric renal disease","volume":"71","author":"Joles","year":"1999","journal-title":"Kidney Int Suppl"},{"key":"2022033100230212300_bib54","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1046\/j.1523-1755.2001.0600031088.x","article-title":"Albumin restores lysophosphatidylcholine-induced inhibition of vasodilation in rat aorta","volume":"60","author":"Vuong","year":"2001","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib55","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/ndt\/gfg238","article-title":"Hypoalbuminaemia enhances the renal vasoconstrictor effect of lysophosphatidylcholine","volume":"18","author":"Vuong","year":"2003","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib56","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/ki.1997.393","article-title":"Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine","volume":"52","author":"Joles","year":"1997","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib57","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbalip.2014.11.010","article-title":"Neutrophil effector responses are suppressed by secretory phospholipase A2 modified HDL","volume":"1851","author":"Curcic","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2022033100230212300_bib58","doi-asserted-by":"crossref","first-page":"158686","DOI":"10.1016\/j.bbalip.2020.158686","article-title":"Lysophosphatidylcholines inhibit human eosinophil activation and suppress eosinophil migration in vivo","volume":"1865","author":"Knuplez","year":"2020","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2022033100230212300_bib59","doi-asserted-by":"crossref","first-page":"N37","DOI":"10.1097\/00003246-200004001-00005","article-title":"Biology of nitric oxide signaling","volume":"28","author":"Liaudet","year":"2000","journal-title":"Crit Care Med"},{"key":"2022033100230212300_bib60","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1073\/pnas.89.1.444","article-title":"S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds","volume":"89","author":"Stamler","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022033100230212300_bib61","doi-asserted-by":"crossref","first-page":"7674","DOI":"10.1073\/pnas.89.16.7674","article-title":"Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin","volume":"89","author":"Stamler","year":"1992","journal-title":"Proc Natl Acad Sci UA"},{"key":"2022033100230212300_bib62","doi-asserted-by":"crossref","first-page":"e00031","DOI":"10.1042\/BSR20120120","article-title":"The contribution of N2O3 to the cytotoxicity of the nitric oxide donor DETA\/NO: an emerging role for S-nitrosylation","volume":"33","author":"Ali","year":"2013","journal-title":"Biosci Rep"},{"key":"2022033100230212300_bib63","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrd2466","article-title":"The nitrate\u2013nitrite\u2013nitric oxide pathway in physiology and therapeutics","volume":"7","author":"Lundberg","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"2022033100230212300_bib64","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1161\/01.RES.0000122071.55721.BC","article-title":"S-nitrosothiols in the blood: roles, amounts, and methods of analysis","volume":"94","author":"Stamler","year":"2004","journal-title":"Circ Res"},{"key":"2022033100230212300_bib65","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1006\/bbrc.1996.1138","article-title":"Albumin is an important vascular tonus regulator as a reservoir of nitric oxide","volume":"225","author":"Minamiyama","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"2022033100230212300_bib66","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1172\/JCI116364","article-title":"NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties","volume":"91","author":"Keaney","year":"1993","journal-title":"J Clin Invest"},{"key":"2022033100230212300_bib67","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1046\/j.1523-1755.2000.00936.x","article-title":"Postischemic vasodilation, endothelial activation, and cardiovascular remodeling in end-stage renal disease","volume":"57","author":"Pannier","year":"2000","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib68","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1046\/j.1523-1755.2002.00483.x","article-title":"Statin therapy improves brachial artery endothelial function in nephrotic syndrome","volume":"62","author":"Dogra","year":"2002","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib69","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1523-1755.2001.00785.x","article-title":"Vascular function of the peripheral circulation in patients with nephrosis","volume":"60","author":"Watts","year":"2001","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib70","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/ki.1995.325","article-title":"Impaired endothelial function in patients with nephrotic range proteinuria","volume":"48","author":"Stroes","year":"1995","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib71","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1093\/ndt\/gfl443","article-title":"Low albumin levels increase endothelial NO production and decrease vascular NO sensitivity","volume":"21","author":"Bevers","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib72","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejphar.2015.01.005","article-title":"Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells","volume":"751","author":"Gremmels","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"2022033100230212300_bib73","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1161\/01.HYP.34.6.1237","article-title":"cGMP-mediated negative-feedback regulation of endothelial nitric oxide synthase expression by nitric oxide","volume":"34","author":"Vaziri","year":"1999","journal-title":"Hypertension"},{"key":"2022033100230212300_bib74","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1172\/JCI115149","article-title":"Fatty acid distribution in systems modeling the normal and diabetic human circulation. A 13C nuclear magnetic resonance study","volume":"87","author":"Cistola","year":"1991","journal-title":"J Clin Invest"},{"key":"2022033100230212300_bib75","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1159\/000168653","article-title":"Contribution of proteinuria to progressive renal injury: consequences of tubular uptake of fatty acid bearing albumin","volume":"13","author":"Thomas","year":"1993","journal-title":"Am J Nephrol"},{"key":"2022033100230212300_bib76","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1089\/152308603764816505","article-title":"Free fatty acid overload attenuates Ca2+ signaling and NO production in endothelial cells","volume":"5","author":"Esenabhalu","year":"2003","journal-title":"Antioxid Redox Signal"},{"key":"2022033100230212300_bib77","doi-asserted-by":"crossref","first-page":"149","DOI":"10.33549\/10.33549\/physiolres.930899","article-title":"Vascular metabolic dysfunction and lipotoxicity","volume":"56","author":"Mattern","year":"2007","journal-title":"Physiol Res"},{"key":"2022033100230212300_bib78","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.lfs.2011.02.022","article-title":"Effects of human serum albumin complexed with free fatty acids on cell viability and insulin secretion in the hamster pancreatic beta-cell line HIT-T15","volume":"88","author":"Tuei","year":"2011","journal-title":"Life Sci"},{"key":"2022033100230212300_bib79","doi-asserted-by":"crossref","first-page":"19709","DOI":"10.1074\/jbc.M209709200","article-title":"Mitochondrial functional state in clonal pancreatic beta-cells exposed to free fatty acids","volume":"278","author":"Koshkin","year":"2003","journal-title":"J Biol Chem"},{"key":"2022033100230212300_bib80","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/ki.1987.151","article-title":"Albumin synthesis, albuminuria and hyperlipemia in nephrotic patients","volume":"31","author":"Kaysen","year":"1987","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib81","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1523-1755.2001.00478.x","article-title":"Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome","volume":"59","author":"Shearer","year":"2001","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib82","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1172\/JCI114750","article-title":"Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat","volume":"86","author":"Davies","year":"1990","journal-title":"J Clin Invest"},{"key":"2022033100230212300_bib83","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.kint.2016.02.026","article-title":"Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences","volume":"90","author":"Vaziri","year":"2016","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib84","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nm.3396","article-title":"Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome","volume":"20","author":"Clement","year":"2014","journal-title":"Nat Med"},{"key":"2022033100230212300_bib85","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.trsl.2014.06.004","article-title":"The proteinuria-hypertriglyceridemia connection as a basis for novel therapeutics for nephrotic syndrome","volume":"165","author":"Clement","year":"2015","journal-title":"Transl Res"},{"key":"2022033100230212300_bib86","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1681\/ASN.2016020200","article-title":"Inhibition of \u03b1v\u03b25 integrin attenuates vascular permeability and protects against renal ischemia-reperfusion injury","volume":"28","author":"McCurley","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2022033100230212300_bib87","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1159\/000020562","article-title":"Molecular interactions between albumin and proximal tubular cells","volume":"6","author":"Brunskill","year":"1998","journal-title":"Exp Nephrol"},{"key":"2022033100230212300_bib88","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000098432","article-title":"Albumin activation of NAD(P)H oxidase activity is mediated via Rac1 in proximal tubule cells","volume":"27","author":"Whaley-Connell","year":"2007","journal-title":"Am J Nephrol"},{"key":"2022033100230212300_bib89","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1053\/ajkd.2001.20733","article-title":"Mechanisms of albumin uptake by proximal tubular cells","volume":"37","author":"Brunskill","year":"2001","journal-title":"Am J Kidney Dis"},{"key":"2022033100230212300_bib90","doi-asserted-by":"crossref","first-page":"e0176198","DOI":"10.1371\/journal.pone.0176198","article-title":"Angiopoietin-like-4 and minimal change disease","volume":"12","author":"Cara-Fuentes","year":"2017","journal-title":"PLoS One"},{"key":"2022033100230212300_bib91","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1111\/j.1523-1755.2004.00044.x","article-title":"Albumin turns on a vicious spiral of oxidative stress in renal proximal tubules","volume":"66","author":"Imai","year":"2004","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib92","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/sj.ki.5001629","article-title":"Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells","volume":"70","author":"Ishola","year":"2006","journal-title":"Kidney Int"},{"key":"2022033100230212300_bib93","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1093\/ndt\/17.10.1751","article-title":"Fatty acids carried on albumin modulate proximal tubular cell fibronectin production: a role for protein kinase C","volume":"17","author":"Arici","year":"2002","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib94","doi-asserted-by":"crossref","first-page":"F851","DOI":"10.1152\/ajprenal.00490.2019","article-title":"Differential kidney proximal tubule cell responses to protein overload by albumin and its ligands","volume":"318","author":"Long","year":"2020","journal-title":"Am J Physiol Renal Physiol"},{"key":"2022033100230212300_bib95","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1681\/ASN.V75728","article-title":"Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease","volume":"7","author":"Foley","year":"1996","journal-title":"J Am Soc Nephrol"},{"key":"2022033100230212300_bib96","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/ndt\/gfx191","article-title":"Albumin handling in different hemodialysis modalities","volume":"33","author":"van Gelder","year":"2018","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib97","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1053\/j.ajkd.2003.08.045","article-title":"Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD","volume":"43","author":"Cooper","year":"2004","journal-title":"Am J Kidney Dis"},{"key":"2022033100230212300_bib98","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0272-6386(00)70200-9","article-title":"C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients","volume":"35","author":"Yeun","year":"2000","journal-title":"Am J Kidney Dis"},{"key":"2022033100230212300_bib99","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/01.SLA.0000055547.93484.87","article-title":"Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials","volume":"237","author":"Vincent","year":"2003","journal-title":"Ann Surg"},{"key":"2022033100230212300_bib100","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1177\/0115426505020003314","article-title":"Albumin therapy in clinical practice","volume":"20","author":"Mendez","year":"2005","journal-title":"Nutr Clin Pract"},{"key":"2022033100230212300_bib101","first-page":"CD001208","article-title":"Human albumin solution for resuscitation and volume expansion in critically ill patients","volume":"11","author":"Albumin","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2022033100230212300_bib102","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s00134-010-2039-6","article-title":"Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis","volume":"37","author":"SAFE Study","year":"2011","journal-title":"Intensive Care Med"},{"key":"2022033100230212300_bib103","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1186\/s13054-014-0702-y","article-title":"Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials","volume":"18","author":"Xu","year":"2014","journal-title":"Crit Care"},{"key":"2022033100230212300_bib104","doi-asserted-by":"crossref","first-page":"g4561","DOI":"10.1136\/bmj.g4561","article-title":"Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality","volume":"349","author":"Patel","year":"2014","journal-title":"BMJ"},{"key":"2022033100230212300_bib105","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJMoa1305727","article-title":"Albumin replacement in patients with severe sepsis or septic shock","volume":"370","author":"Caironi","year":"2014","journal-title":"N Engl J Med"},{"key":"2022033100230212300_bib106","doi-asserted-by":"crossref","first-page":"205","DOI":"10.12659\/AOT.889188","article-title":"Human albumin: old, new, and emerging applications","volume":"18","author":"Rozga","year":"2013","journal-title":"Ann Transplant"},{"key":"2022033100230212300_bib107","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41581-020-00384-1","article-title":"Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN working group","volume":"17","author":"Boyer","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2022033100230212300_bib108","doi-asserted-by":"crossref","first-page":"820","DOI":"10.2215\/CJN.09670620","article-title":"Intravenous albumin for mitigating hypotension and augmenting ultrafiltration during kidney replacement therapy","volume":"16","author":"Hryciw","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022033100230212300_bib109","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/IJNRD.S291348","article-title":"Slipping through the pores: hypoalbuminemia and albumin loss during hemodialysis","volume":"14","author":"Kalantar-Zadeh","year":"2021","journal-title":"Int J Nephrol Renovasc Dis"},{"key":"2022033100230212300_bib110","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/ndt\/gfy236","article-title":"Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?","volume":"34","author":"Ward","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib111","first-page":"CD009692","article-title":"Human albumin infusion for treating oedema in people with nephrotic syndrome","volume":"7","author":"Ho","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2022033100230212300_bib112","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/ndt\/11.7.1224","article-title":"Does it make sense to administer albumin to the patient with nephrotic oedema?","volume":"11","author":"Dorhout Mees","year":"1996","journal-title":"Nephrol Dial Transplant"},{"key":"2022033100230212300_bib113","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/cc13991","article-title":"Albumin administration in the acutely ill: what is new and where next?","volume":"18","author":"Vincent","year":"2014","journal-title":"Crit Care"},{"key":"2022033100230212300_bib114","doi-asserted-by":"crossref","first-page":"820","DOI":"10.2215\/CJN.09670620","article-title":"Intravenous albumin for mitigating hypotension and augmenting ultrafiltration during kidney replacement therapy","volume":"16","author":"Hryciw","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022033100230212300_bib115","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: pathogenesis and clinical significance","volume":"43","author":"Soeters","year":"2019","journal-title":"JPEN J Parenter Enteral Nutr"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfab194\/42098011\/sfab194.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/15\/4\/624\/43058011\/sfab194.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/15\/4\/624\/43058011\/sfab194.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T20:24:34Z","timestamp":1648671874000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/15\/4\/624\/6381728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":115,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,10,5]]},"published-print":{"date-parts":[[2022,3,31]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfab194","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4]]},"published":{"date-parts":[[2021,10,5]]}}}