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
Khajohn Tiranathanagul,
1,2
Sukgasem Amornsuntorn,
3
Yingyos Avihingsanon,
1
Nattachai Srisawat,
1,2
Paweena Susantitaphong,
1
Kearkiat Praditpornsilpa,
1
Kriang Tungsanga,
1
and Somchai Eiam-Ong
1
1
Division of Nephrology, Department of Medicine,
2
Excellence Center for Critical Care Nephrology, King
Chulalongkorn Memorial Hopital, Thai Red Cross Society and Faculty of Medicine, Chulalongkorn University,
Bangkok, and
3
Department of Medicine, Prachuap Khiri Khan Hospital, Prachuap Khiri Khan, Thailand
Abstract: Delayed initiation of renal replacement therapy
(RRT) in critically ill acute kidney injury (AKI) patients
results in high mortality while too early RRT causes unnec-
essary risks of the treatment. Current traditional indications
cannot clearly identify the appropriate time for initiating
RRT.This prospective cohort study was conducted to deter-
mine 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 con-
clusion, 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. Key Words: Acute
kidney injury, Biomarker, Neutrophil gelatinase-associated
lipocalin, Renal replacement therapy.
Critically ill patients who adversely develop severe
acute kidney injury (AKI) and require renal replace-
ment therapy (RRT) are associated with substan-
tially high morbidity and mortality.The mortality rate
is more than 50% and increases to 80% in sepsis
patients (1,2). This undesired result still persists
despite the advancement in RRT modalities. One
possible explanation is the proper timing of RRT
initiation. Initiation of RRT according to traditional
indications might be too late and results in worse
outcomes. Emerging data suggest that earlier RRT
initiation may attenuate kidney as well as distant
non-kidney organ injury from uremia, acidemia, fluid
overload, and systemic inflammation (3). On the con-
trary, too early initiation of RRT causes unnecessary
risks of treatment. Moreover, some early RRT-
initiated patients might recover with conservative
treatment alone (4). Unfortunately, traditional serum
biomarkers or urine output volume cannot clearly
define early/late distinction (5).
Received June 2012; revised October 2012.
Address correspondence and reprint requests to Dr Khajohn
Tiranathanagul, Division of Nephrology, Department of Medicine,
Faculty of Medicine, King Chulalongkorn Memorial Hospital,
Chulalongkorn University, Bangkok 10330, Thailand. Email:
khajohn.t@chula.ac.th
Presented in part at the American Society of Nephrology Renal
Week 2011, held November 8–13, 2011 in Philadelphia, PA, USA.
Therapeutic Apheresis and Dialysis 2013; 17(3):332–338
doi: 10.1111/1744-9987.12004
© 2013 The Authors
Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis
332