title: Neutrophil gelatinase-associated lipocalin (NGAL) in chronic cardiorenal failure is correlated with endogenous erythropoietin levels and decreases in response to low-dose erythropoietin treatment.
abstract: BACKGROUND
  Neutrophil-gelatinase associated lipocalin (NGAL), a tubular injury marker, is associated with iron metabolism in hemodialysis patients. We investigated whether serum NGAL levels reflect iron metabolism in combined chronic heart failure and chronic kidney disease (CHF/CKD) and whether treatment with low-dose erythropoietin stimulating agent (ESA) modulates NGAL levels.
  
  
  METHODS
  In the EPOCARES trial (ClinTrialsNCT00356733) serum NGAL, hepcidin-25, transferrin saturation (TSAT), reticulocyte hemoglobin content (Ret-He) and endogenous erythropoietin (EPO) levels were measured.
  
  
  RESULTS
  Baseline serum NGAL levels correlated with cystatin C (r=0.767, p<0.001) and baseline EPO levels (r=-0.395, p=0.003). There was no correlation with baseline TSAT, Ret-He, and hepcidin-25 levels. After two weeks, NGAL levels decreased in the ESA-group (p=0.02), while there was no change in the no-ESA group (p=0.62). The magnitude in NGAL decrease in the ESA-group correlated with baseline EPO levels (r=0.431, p=0.01).
  
  
  CONCLUSIONS
  In contrast to in HD patients, in combined CKD/ CHF, serum NGAL levels did not correlate with iron metabolism, hence NGAL might reflect tubular damage in these patients. NGAL levels inversely correlated with baseline EPO levels and decreased in response to short-term ESA treatment, which might reflect an effect of ESA on tubular damage. These findings need to be confirmed and alternative explanations should be evaluated.
authors.affiliation: Department of Cardiology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Mireille E
authors.initials: ME
authors.lastname: Emans
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.forename: Adry
authors.initials: A
authors.lastname: Diepenbroek
authors.forename: Karien
authors.initials: K
authors.lastname: van der Putten
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Cramer
authors.forename: Jos P M
authors.initials: JP
authors.lastname: Wielders
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Gaillard
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology; D014168:Transferrin / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D064451:Hepcidins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014168:Transferrin; C545475:hepcidin 25, human; D004921:Erythropoietin; D007501:Iron