Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage

Abstract

Purpose: 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.

Keywords: Combination of biomarkers; Prediction; Renal replacement therapy; Urinary neutrophil gelatinase–associated lipocalin.