title: Influence of severity of illness on neutrophil gelatinase-associated lipocalin performance as a marker of acute kidney injury: a prospective cohort study of patients with sepsis.
abstract: BACKGROUND
  The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can be negatively impacted by severity of illness and inflammation, and that both uNGAL and sNGAL levels can be increased regardless of presence of AKI.
  
  
  METHODS
  One hundred and seven patients with sepsis were included. uNGAL and sNGAL were measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient and intrinsic AKI were respectively defined as AKI according to RIFLE during the first 72 hours that did or did not recover to "no AKI" in the following 72 hours. Patients were classified according to tertiles of CRP and APACHE II score increase. The relationship between sNGAL and uNGAL was assessed by linear regression.
  
  
  RESULTS
  Fifty-seven patients developed transient and 22 intrinsic AKI. Prevalence of transient and intrinsic AKI were higher in patients with versus without septic shock (OR (95% CI): 3.3(1.4-8.2)). uNGAL was associated with sNGAL, and this with parallel slopes but different intercepts for AKI (Y = 0.87*X + 314.3, R2 = 0.31) and no AKI (Y = 0.87*X + 20.1, R2 = 0.38). At T4, median uNGAL and sNGAL levels were higher in septic patients with versus without shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474 ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels increased with tertiles of CRP and APACHE II score increase.
  
  
  CONCLUSIONS
  Serum and uNGAL levels are influenced by severity of illness and inflammation, and this was found to be independent of the presence of AKI. There is a strong correlation between sNGAL and uNGAL levels in patients with sepsis, indicating that increased levels of uNGAL can also be due to overspill from the systemic circulation, blurring the discriminative value of NGAL as a biomarker for AKI in patients with sepsis.
authors: Jill
authors: J
authors: Vanmassenhove
authors: Griet
authors: G
authors: Glorieux
authors: Norbert
authors: N
authors: Lameire
authors: Eric
authors: E
authors: Hoste
authors: Annemieke
authors: A
authors: Dhondt
authors: Raymond
authors: R
authors: Vanholder
authors: Wim
authors: W
authors: Van Biesen
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000150:complications / Q000652:urine*; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018570:Risk Assessment; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000652:urine*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins