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

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. 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). 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). 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.

Pipili C ，Ioannidou S ，Tripodaki ES ，Parisi M ，Douka E ，Vasileiadis I ，Joannidis M ，Nanas S ... -  《-》

Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study.

The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a -30-day composite clinical outcome (RRT - or death). A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

McMahon BA ，Galligan M ，Redahan L ，Martin T ，Meaney E ，Cotter EJ ，Murphy N ，Hannon C ，Doran P ，Marsh B ，Nichol A ，Murray PT ... -  《-》

Evaluation of clinically available renal biomarkers in critically ill adults: a prospective multicenter observational study.

Deng Y ，Chi R ，Chen S ，Ye H ，Yuan J ，Wang L ，Zhai Y ，Gao L ，Zhang D ，Hu L ，Lv B ，Long Y ，Sun C ，Yang X ，Zou X ，Chen C ... -  《CRITICAL CARE》

Potential role of neutrophil gelatinase-associated lipocalin in identifying critically ill patients with acute kidney injury stage 2-3 who subsequently require renal replacement therapy.

Delayed initiation of renal replacement therapy (RRT) in critically ill acute kidney injury (AKI) patients results in high mortality while too early RRT causes unnecessary risks of the treatment. Current traditional indications cannot clearly identify the appropriate time for initiating RRT. This prospective cohort study was conducted to determine the accuracy of using plasma neutrophil gelatinase-associated lipocalin (pNGAL) and urine NGAL (uNGAL) in early identifying of the AKI patients who subsequently required RRT. Forty-seven critically ill patients with AKI stage 2-3 who did not reach the traditional indications for RRT were enrolled in this study. The pNGAL, uNGAL, and other parameters were determined in each patient. The primary end point was RRT initiation according to the traditional indications within 3 days. The mean age of the patients was 63.0 ± 18.1 years. pNGAL could predict subsequent RRT requirements with area under ROC 0.813 (P < 0.001, 95%CI 0.66-0.90). The cut-off point of 960 ng/mL provided sensitivity and specificity of 72.2 and 89.6%, respectively, and positive and negative predictive values of 81.25% and 83.8%, respectively. The uNGAL provided slightly lower significance of statistical parameters. The combination of pNGAL level of 960 ng/mL and APACHE II score of 20 improved statistical values. In conclusion, pNGAL is an excellent early biomarker for RRT initiation in critically ill patients with AKI stage 2-3. The pNGAL value of 960 ng/mL, alone or in combination with APACHE II score might be used as the early new indicator for early initiation of RRT in AKI stage 2-3 and this might improve patient survival.

Tiranathanagul K ，Amornsuntorn S ，Avihingsanon Y ，Srisawat N ，Susantitaphong P ，Praditpornsilpa K ，Tungsanga K ，Eiam-Ong S ... -  《-》

Biomarkers upon discontinuation of renal replacement therapy predict 60-day survival and renal recovery in critically ill patients with acute kidney injury.

There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60-day survival and renal recovery in an effort to add knowledge to the decision-making process regarding RRT withdrawal. We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL-6), serum cystatin C (sCysC), sIL-18, serum neutrophil gelatinase-associated lipocalin and urinary IL-18 and urinary neutrophil gelatinase-associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013-1.047, P = 0.001), diabetes (OR 23.157, 95% CI 4.507-118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121-1.527, P = 0.001) were independent predictors of 60-day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25- and 2.31-fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P = 0.026) and an integrated discriminative index of 0.155 (P = 0.032). Lower levels of sOPN and sIL-6 were associated with greater odds of 60-day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60-day renal recovery with the greatest AUC of 0.743. Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60-day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL-6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.

Yang T ，Sun S ，Zhao Y ，Liu Q ，Han M ，Lin L ，Su B ，Huang S ，Yang L ... -  《-》