title: Serum uromodulin-a marker of kidney function and renal parenchymal integrity.
abstract: An ELISA to analyse uromodulin in human serum (sUmod) was developed, validated and tested for clinical applications.
  
  
  
  We assessed sUmod, a very stable antigen, in controls, patients with chronic kidney disease (CKD) stages 1-5, persons with autoimmune kidney diseases and recipients of a renal allograft by ELISA.
  
  
  
  Median sUmod in 190 blood donors was 207 ng/mL (women: men, median 230 versus 188 ng/mL, P = 0.006). sUmod levels in 443 children were 193 ng/mL (median). sUmod was correlated with cystatin C (rs = -0.862), creatinine (rs = -0.802), blood urea nitrogen (BUN) (rs = -0.645) and estimated glomerular filtration rate (eGFR)-cystatin C (rs  =  0.862). sUmod was lower in systemic lupus erythematosus-nephritis (median 101 ng/mL), phospholipase-A2 receptor- positive glomerulonephritis (median 83 ng/mL) and anti-glomerular basement membrane positive pulmorenal syndromes (median 37 ng/mL). Declining sUmod concentrations paralleled the loss of kidney function in 165 patients with CKD stages 1-5 with prominent changes in sUmod within the 'creatinine blind range' (71-106 µmol/L). Receiver-operating characteristic analysis between non-CKD and CKD-1 was superior for sUmod (AUC 0.90) compared with eGFR (AUC 0.39), cystatin C (AUC 0.39) and creatinine (AUC 0.27). sUmod rapidly recovered from 0 to 62 ng/mL (median) after renal transplantation in cases with immediate graft function and remained low in delayed graft function (21 ng/mL, median; day 5-9: relative risk 1.5-2.9, odds ratio 1.5-6.4). Immunogold labelling disclosed that Umod is transferred within cytoplasmic vesicles to both the apical and basolateral plasma membrane. Umod revealed a disturbed intracellular location in kidney injury.
  
  
  
  We conclude that sUmod is a novel sensitive kidney-specific biomarker linked to the structural integrity of the distal nephron and to renal function.
authors.affiliation: Klinikum München-Harlaching, Teaching Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Scherberich
authors.affiliation: Krankenhaus Barmherzige Brüder, Teaching Hospital of the University of Regensburg, Regensburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gruber
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Philipps-University, Marburg, Germany.
authors.forename: Wolfgang Andreas
authors.initials: WA
authors.lastname: Nockher
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Erik Ilsø
authors.initials: EI
authors.lastname: Christensen
authors.affiliation: Nephrology Outpatient Clinic, Dortmund, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Schmitt
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Herbst
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Block
authors.affiliation: Kidney Transplant Centre, Municipal Hospital Berlin-Friedrichshain, Teaching Hospital of the Charité Berlin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kaden
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlumberger
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000097:blood / Q000473:pathology*; D006470:Hemorrhage / Q000097:blood / Q000473:pathology*; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000097:blood / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000473:pathology*; D008181:Lupus Nephritis / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000473:pathology*; D058949:Uromodulin / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055316:Cystatin C; C548612:UMOD protein, human; D058949:Uromodulin; D003404:Creatinine
keywords: kidney failure; renal biomarker; serum assay; thick ascending limb; uromodulin