title: Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage.
abstract: OBJECTIVE
  Mechanically ventilated critically ill patients with high severity score indices need a very cautious therapeutic approach. Considering that inappropriate decisions on renal replacement therapy (RRT) initiation may promote unwanted adverse effects, we evaluated whether a panel of novel and traditional renal markers is superior to conventional renal marker in predicting RRT requirements in this group of patients.
  
  
  METHODS
  This was a prospective observational study, performed at the two distinct multidisciplinary intensive care units (ICUs) of a 1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled the inclusion criteria of the study. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were determined on ICU admission. The predictive performance of all markers for first RRT was tested and compared based on the area under the receiver operating characteristic (ROC) curves. Time-dependent ROC curves were used to assess the earlier time point where the markers presented their maximum area under the curve (AUC).
  
  
  RESULTS
  All studied biomarkers and acute physiology and chronic health evaluation (APACHE) II score, were significant independent predictors of RRT (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC and sCr showed early maximum predictive ability within 10 days of ICU admission, while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients without acute kidney injury (AKI) on ICU entry, the combination of sCysC and APACHE II score proved best (AUC-ROC=0.78).
  
  
  CONCLUSIONS
  Specific markers of kidney dysfunction and of kidney damage can be successfully combined to increase the prognostic capability for RRT initiation. The presence of AKI affects diagnostic performance. Without an established AKI on ICU admission, future RRT requirement was better predicted by the combination of illness severity with a marker of glomerular filtration rate. With AKI on ICU admission a combination of the marker of glomerular filtration rate with one of tubular injury proved best.
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Pipili
authors.affiliation: Laboratory of Biochemistry, 'Evangelismos' Hospital, Athens, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Ioannidou
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Elli-Sophia
authors.initials: ES
authors.lastname: Tripodaki
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Parisi
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Douka
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vasileiadis
authors.affiliation: Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Joannidis
authors.affiliation: First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: a.icusn@gmail.com.
authors.forename: Serafim
authors.initials: S
authors.lastname: Nanas
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy*; D000209:Acute-Phase Proteins; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016638:Critical Illness; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D017582:Renal Replacement Therapy; D012121:Respiration, Artificial; D012720:Severity of Illness Index
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C
keywords: Combination of biomarkers; Prediction; Renal replacement therapy; Urinary neutrophil gelatinase–associated lipocalin