EXPERIMENTAL AND THERAPEUTIC MEDICINEUrinary neutrophil gelatinase-associated lipocalin is an early
predictor of acute kidney injury in premature infants
RYOTA KURIBAYASHI1, HIROSHI SUZUMURA1, TOSHIMI SAIRENCHI2, YOSHIYUKI WATABE1,YAYOI TSUBOI1, GEORGE IMATAKA1, HIDEMITSU KUROSAWA1 and OSAMU ARISAKA1
Departments of 1Pediatrics and 2Public Health, Dokkyo Medical
University School of Medicine, Mibu, Tochigi 321‑0293, Japan
Received September 5, 2016; Accepted October 20, 2016
DOI: 10.3892/etm.2016.3837
Abstract. Urinary neutrophil gelatinase‑associated lipocalin(uNGAL) is produced in response to tubular epithelial injury
and is a biomarker of tubulointerstitial injury. The aim of thepresent study was to examine whether acute kidney injury(AKI) could be predicted by measuring uNGAL in very
low‑birth weight (VLBW) infants. Forty VLBW infants withbirthweight below 1,500 g were enrolled in the present study.
uNGAL and serum creatinine (sCre) were measured daily
from postnatal days 0 to 8. Infants with sCre ≥1.2 mg/dl werediagnosed with AKI. The relationship of uNGAL with sCre
was measured on the day after uNGAL measurement (next‑daysCre) was examined. The results showed that 16 infants had
sCre ≥1.2 mg/dl in this period. Logistic regression analysis
revealed that uNGAL on postnatal days 2, 3, 4, 5 and 6 wascorrelated with next‑day sCre (P<0.05). uNGAL corrected byurinary Cre (uCre) (uNGAL/uCre) was only correlated with anincrease in next‑day sCre on postnatal days 5 and 6 (P<0.05).
For the logistic analysis, subjects with high and low uNGAL
levels based on the median value for each day, uNGAL on post‑
natal days 2, 3 and 6 in the high uNGAL group was correlatedwith an increase in next‑day sCre. Thus, AKI may be predictedby measuring uNGAL in VLBW infants. This measurement
was non‑invasive, and is potentially useful for the evaluation ofrenal function in VLBW infants.
Introduction
Renal function is immature in premature infants, and this caneasily result in the development of acute kidney injury (AKI)
due to changes in blood pressure and respiratory conditions,as well as administration of some drugs. It has been found that

8‑24% of premature infants admitted to a neonatal intensive
care unit (NICU) develop AKI (1,2). Additionally, AKI may
contribute to the mortality of very low‑birth weight (VLBW)
infants with a birth weight of <1,500 g (3). Serum creatinine(sCre) is often used as a biomarker for renal function, albeit
it is affected by parameters including muscle mass, gender,
ethnicity, and medication (4). Additionally, several days
are usually required before an increase in sCre level can bedetected in infants with AKI (5).
Neutrophil gelatinase‑associated lipocalin (NGAL) is a
25‑kDa protein from the lipocalin family that is primarily
secreted by activated neutrophils (6). NGAL is produced in
the granules of activated neutrophils and also by the nephronin response to any damage to tubular epithelium; therefore,
NGAL can serve as a biomarker for tubulointerstitial injury (7).
When the kidney is damaged, NGAL is mainly producedin the ascending thick limb of the loop of Henle and renalcollecting tubule, and is immediately secreted into urine (8).
Urinary NGAL (uNGAL) is increased with renal ischemia
and associated acute tubular necrosis (9), and thus uNGAL
is useful for the prediction of renal failure (10). uNGAL may
also be an early marker of renal failure in adults and children
after cardiac surgery or renal transplantation (11,12), andmay be useful in the detection of chronic kidney failure inchildren (13), as well as the prediction of bronchopulmonary
dysplasia in premature infants (14). The standard range ofuNGAL in newborns, particularly VLBW infants, has beensuggested to range between 2 and 150 ng/ml (15), albeit thishas not been clearly established (16).
In the present study, we investigated whether an increaseof uNGAL was useful for the early prediction of renal failure
in VLBW infants.
Materials and methods

Correspondence to: Dr Ryota Kuribayashi, Department ofPediatrics, Dokkyo Medical University School of Medicine,
880 Kitakobayashi, Mibu, Tochigi 321‑0293, JapanE‑mail: r‑kuri@dokkyomed.ac.jp

Key words: acute kidney injury, prediction, serum creatinine,urinary NGAL, very low‑birth weight infant

Subjects. The study subjects were infants who were bornwith a gestational age of 23 to <32 weeks and a birthweight of 500‑1,500 g, and were admitted to the NICU of
Dokkyo Medical University Hospital from January, 2009 to
December, 2010. Infants with chromosomal abnormalities,
external deformities and those with life‑threatening diseases
were excluded. Subsequently, a prospective single‑center study
was performed.

2

KURIBAYASHI et al: EARLY PREDICTION OF ACUTE KIDNEY INJURY USING uNGAL

Table I. Infant and maternal characteristics.
Characteristics
Gestational age (weeks)aBirthweight (g)aNormal spontaneous delivery (%)
1‑min Apgara
5‑min Apgara
Female (%)
Antenatal steroids (%)
Chorioamnionitis (%)
Indomethacin (%)
Aminoglycoside (%)
Mechanical ventilation (%)

sCre ≥1.2 mg/dl (n=16)

sCre <1.2 mg/dl (n=24)

P‑value26.3±1.9845±251
7 (44)
4.0±2.1
6.9±1.1
9 (56)
9 (56)
11 (69)12 (75)14 (88)11 (69)27.6±2.0
1,055±252
14 (58)5.6±2.1
7.8±1.7
10 (42)18 (75)16 (67)
12 (50)16 (67)8 (33)

0.030
0.013
0.520
0.030
0.029
0.520
0.305
1.000
0.188
0.263
0.051

Mean ± standard deviation. sCre, serum creatinine.

aThis study was performed after obtaining approval fromthe ethics committee of Dokkyo Medical University (approval
no. 25042) and informed consent from the infants' parents.

aminoglycoside antibiotics were used, as well as mechanicalventilation, antenatal steroid therapy, delivery method, andonset of chorioamnionitis for the diagnosis of AKI (17).

Methods. uNGAL and sCre levels were measured daily frompostnatal days 0 to 8. For the measurement of uNGAL, urine
was collected using cotton balls or a urine sampling bag andthe samples were stored at ‑80˚C. When urine was collectedwith a cotton ball, the ball was applied to the vulva in the diaper
and was collected after it was immersed in urine. uNGAL andurinary Cre (uCre) levels were unaffected by the measurement
method (17,18). Furthermore, measurements of uNGAL levels
in 23 subjects using urine sampling bags and cotton balls
produced values of 134.5±128 and 132.1±125 ng/ml, respec‑tively, with no significant difference (P=0.95). Based on these
data, we collected urine using one of these methods.
uNGAL was measured using an NGAL ELISA kit 036(BioPorto Diagnostics, Gentofte, Denmark) that specifi‑
cally detects human NGAL. The urine sample was diluted
500 times using dilution solution provided in the NGAL kit.
NGAL standards or diluted samples (100 µl) were applied toprecoated microwells in duplicate, incubated for 1 h at 23±2˚C,
and washed with washing buffer. Subsequently, biotinylated
NGAL antibody and HRP‑streptavidin were added to wells andincubated for 1 h via centrifugation using a shaking platform(200 rpm; Taiyo Micromixer, Taiyo Science Industrial Co. Ltd.,Tokyo, Japan). TMB substrate was added for 10 min in the dark
prior to adding stop solution. The NGAL concentration was thenmeasured at 450 nm wavelength in each well with a reference
reading at 620 nm in blank wells. The average was considered tobe the uNGAL value. uCre was measured in the same samples.
sCre is generally used as an index of renal dysfunctionin the first postnatal month (16) and is obtained using blood
samples obtained in daily medical routine tests. AKI isdiagnosed based on sCre ≥1.2 mg/dl (17). Subjects with sCrelevels of ≥1.2 and <1.2 mg/dl were compared using U tests forgestational age, birth weight, and Apgar score, and Chi‑square
tests for gender. Indomethacin was employed for the treat‑ment of patent ductus arteriosus in immature infants, andStatistical analysis. SPSS 11.0J for Windows (SPSS, Inc.,
Chicago, IL, USA) software was used for statistical analysis.
Logistic regression analyses were performed for uNGAL anduNGAL/uCre with next‑day sCre. Subjects were divided into
low and high uNGAL groups based on the median uNGAL levelon each day. Logistic regression analysis was then performed
to calculate the odds ratio for next‑day sCre as a predictor ofhigh uNGAL, with the value for the low uNGAL group set to 1.
Similar analyses were conducted for uNGAL/uCre. P<0.05 wasconsidered to indicate a statistically significant difference.
Results
Subjects were stratified based on their weight into fourgroups: i) 500‑750 g group (n=9); ii) 751‑1,000 g group (n=15);iii) 1,001‑1,250 g group (n=8); and iv) 1,251‑1,500 g group(n=8). The gestational ages ranged from 23 weeks and 0 days
to <26 weeks (n=13), 26 weeks and 0 days to <29 weeks(n=18), and 29 weeks and 0 days to <32 weeks (n=9). During
the study period, 16 subjects had sCre ≥1.2 mg/dl. Groups
with sCre ≥1.2 and <1.2 mg/dl had significant differences ingestational age, birthweight, and 1‑ and 5‑min Apgar scores,
but no significant differences in gender, delivery method, useof antenatal steroids, chorioamnionitis, use of indomethacin,use of aminoglycoside antibiotics, or mechanical ventilation
were detected (Table I).
uNGAL levels measured in all subjects on postnataldays 0 to 8 are shown in Fig. 1. The median uNGAL washigher than the reported standard value in VLBW infants.
There were significant differences in uNGAL between post‑
natal days 1 and 2, and between postnatal days 2 and 3 (Fig. 1).
Based on logistic regression analysis, an increase in next‑daysCre was significantly correlated with uNGAL on postnataldays 2, 3, 4, 5 and 6 (P<0.05), but with uNGAL/uCre only on
postnatal days 5 and 6 (P<0.05).

EXPERIMENTAL AND THERAPEUTIC MEDICINE

3

Table II. Logistic analysis of uNGAL and next-day serum creatinine.
uNGAL (ng/ml)

Postnatal

No.

Day 0
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8

23
40
40
40
40
40
40
40
17

-------------------------------------------------------------------------------

Low

5.9-167.7
6.6-193.2
15.8-288.5
14.3-359.6
18.6-326.2
17.0-239.9
15.6-233.7
15.0-237.6
158.6-298.9

High

Odds ratio

167.8-499.0	-	
193.3-542.1
3.00 (0.51-17.74)
288.6-541.4
7.36 (1.34-40.55)
359.7-572.6
15.52 (1.73-139.26)
326.3-551.8	-	240.0-542.2	-	
233.8-541.0
10.23 (1.12-93.34)
237.7-542.0
6.33 (0.67-60.16)
299.0-462.3	-	P-valuea
0.744
0.063
0.009
0.010
0.013
0.011
0.004
0.122
0.463

-, indicates no data because there were no cases with increased serum creatinine in the low group, and thus logistic regression analysis was notpossible. aUrinary neutrophil gelatinase‑associated lipocalin (uNGAL) was included as a continuous, rather than a categorical, variable in thelogistic regression model.

Table III. Logistic analysis of uNGAL/uCre and next-day sCre.
uNGAL/uCre

Postnatal

No.

Day 0
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8

23
40
40
40
40
40
40
40
17

-----------------------------------------------------------------------

Low

1.0-19.4
0.8-18.9
1.6-26.0
0.9-21.2
1.6-24.6
1.7-18.1
1.7-20.4
1.3-21.5
9.5-22.7

High

Odds ratio

19.5-95.7	-	
19.0-82.4
1.42 (0.27-7.34)
26.1-61.8
2.15 (0.52-9.00)
21.3-73.1
3.05 (0.66-14.13)
24.7-53.6	-	
18.2-52.6
8.14 (0.88-75.48)
20.5-64.9
3.86 (0.67-22.11)
21.6-78.0
2.53 (0.41-15.75)
22.8-65.1	-	P-valuea
0.486
0.228
0.144
0.159
0.110
0.031
0.014
0.065
0.524

-, indicates no data because there were no cases with increased sCre in the low group, and thus logistic regression analysis was not possible.
auNGAL/uCre was included as a continuous, rather than a categorical, variable in the logistic regression model. uNGAL, urinary neutrophil
gelatinase‑associated lipocalin; uCre, urinary creatinine; sCre, serum Cre.

Figure 1. Urinary neutrophil gelatinase‑associated lipocalin in infants on postnatal days 0 to 8. *P= 0.02 for day 1 vs. day 2, and day 2 vs. day 3 by Mann‑Whitney
U test. NS, not significant.

4

KURIBAYASHI et al: EARLY PREDICTION OF ACUTE KIDNEY INJURY USING uNGAL

Subjects were also divided into low and high uNGAL
groups based on the median uNGAL measured each day.
Calculation of the odds ratio showed that next‑day sCre wasa predictor of high uNGAL on postnatal days 2, 3 and 6(Table II). No relationship with next‑day sCre was detected for
uNGAL/uCre on any day (Table III).
Discussion
The results of the present study have shown that, subjects
with lower gestational age, lower birth weight, and lower
1‑ and 5‑min Apgar scores had increased levels of sCre.
Similar results were reported in previous studies (19,20).
These results were consistent with findings showing that
AKI occurs in 47‑61% of cases of neonatal asphyxia with a5‑min Apgar score of <7 (20‑22). It has been suggested that,compared to sCre, acute renal dysfunction in pediatric patients
may be diagnosed more quickly based on NGAL in urine orblood after cardiac surgery (11). It was also reported that renal
failure may be predicted more precisely with uNGAL because
compared to blood NGAL levels, there was a marked increase
in uNGAL levels (11). Thus, uNGAL is a more effective
marker for renal dysfunction in children (11).
Higher levels of uNGAL have been detected in VLBW
infants with a lower birth weight and lower gestationalage (17), as well as in those with onset of AKI (23,24). The
results showed that, uNGAL levels in the current study werehigher than the recently reported standard value in VLBW
infants (15,25). This difference may be explained by the factthat there were many premature infants with a gestational age<27 weeks among our subjects.
Next‑day sCre, rather than sCre on the day of uNGAL
measurement, was found to be a predictor for uNGAL. A
difference in correlations of uNGAL with uNGAL/uCre andsCre were found (26), but our results support those of previous
studies showing that correction of uNGAL with uCre was notnecessary (15,17,27). An increase in uNGAL (a marker ofproximal tubular epithelium disorder) may occur before an
increase in sCre (a marker of glomerular disorder), because
nephrogenic renal dysfunction may develop when prerenal
failure is protracted (28). Additionally, Cre excreted due totubular disorder may be reabsorbed due to insufficient tubularfunction, which can cause an increase in sCre in infants with
LBW (29,30). uNGAL is excreted from renal proximal tubularcells as a response to AKI (31) and nephrogenic injury (32),and is increased in patients with late‑onset sepsis (33).
uNGAL is not correlated with sCre in VLBW infants (16),however, our results suggested that uNGAL was a usefulbiomarker for the early diagnosis of renal failure in prema‑ture infants by predicting an increase in next‑day sCre. The
increase in sCre levels was significant in the high uNGAL
group, and thus this group was likely to be at risk for AKI.
Further studies using bigger samples are needed to estab‑lish standard daily uNGAL levels for early postnatal days.
Measurement of uNGAL has the advantage of being non‑inva‑
sive for VLBW infants, and use of uNGAL in clinical practice
may allow the prediction of renal failure, control of water
intake, control of dosage of antibiotics that may induce renal
failure, such as aminoglycosides and vancomycin for MRSA,
and the need for use of indomethacin.

The most significant shortcoming of the present study wasthat we were not able to completely collect the maternal sCredata samples. This was because the sCre level of neonates 0 to
3 days after birth were influenced by the maternal sCre throughthe placenta, and data were not reflected adequately (34‑36). In
retrospect, this aspect should have been taken into consider‑ation. Furthermore, because we only evaluated the relationshipbetween uNGAL and sCre, the correlation with AKI was poor.
We cannot disregard the possibility that AKI was overvalued.
However, our results indicate that there was a correlation
between uNGAL and sCre in VLBW infants, because it had
the potential to function as the basic data for additional studies
in the future. More clinical and basic studies on NGAL havebeen reported recently (37‑43). In summary, more research on
the biological mechanism of the NGAL is necessary.
Acknowledgements
The present study was supported by Grants‑in‑Aid for The
Morinaga Foundation for Health and Nutrition. We would
like to express our gratitude and appreciation to the entire
Department of Pediatrics and NICU medical staff, Dokkyo
Medical University Hospital, Tochigi, Japan.
References
1. Hentschel R, Lödige B and Bulla M: Renal insufficiency in the
neonatal period. Clin Nephrol 46: 54‑58, 1996.
2. Stapleton FB, Jones DP and Green RS: Acute renal failure inneonates: Incidence, etiology and outcome. Pediatr Nephrol 1:
314‑320, 1987.
3. Askenazi DJ, Griffin R, McGwin G, Carlo W and Ambalavanan N:
Acute kidney injury is independently associated with mortality
in very low birthweight infants: A matched case‑control analysis.
Pediatr Nephrol 24: 991‑997, 2009.
4. Askenazi DJ, Ambalavanan N and Goldstein SL: Acute kidney
injury in critically ill newborns: What do we know? What do weneed to learn? Pediatr Nephrol 24: 265‑274, 2009.
5. Jo SK, Rosner MH and Okusa MD: Pharmacologic treatment of
acute kidney injury: Why drugs haven't worked and what is on
the horizon. Clin J Am Soc Nephrol 2: 356‑365, 2007.
6. Soni SS, Pophale R and Ronco C: New biomarkers for acute renal
injury. Clin Chem Lab Med 49: 1257‑1263, 2011.
7. Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H,
Saito Y, Yoshioka T, Ogawa Y, Imamaki H, Kusakabe T, et al:
Urinary neutrophil gelatinase‑associated lipocalin levels reflect
damage to glomeruli, proximal tubules, and distal nephrons.
Kidney Int 75: 285‑294, 2009.
8. Gonzalez F and Vincent F: Biomarkers for acute kidney injury
in critically ill patients. Minerva Anestesiol 78: 1394‑1403, 2012.
9. Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J
and Devarajan P: Amelioration of ischemic acute renal injury byneutrophil gelatinase‑associated lipocalin. J Am Soc Nephrol 15:3073‑3082, 2004.
10. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J,
Schmidt‑Ott KM, Chen X, Li JY, Weiss S, et al: Endocytic
delivery of lipocalin‑siderophore‑iron complex rescues thekidney from ischemia‑reperfusion injury. J Clin Invest 115:
610‑621, 2005.
11. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C,
Ruff SM, Zahedi K, Shao M, Bean J, et al: Neutrophil gela‑
tinase‑associated lipocalin (NGAL) as a biomarker for acuterenal injury after cardiac surgery. Lancet 365: 1231‑1238, 2005.
12. Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J,
Edelstein CL and Devarajan P: Urine NGAL and IL‑18 are
predictive biomarkers for delayed graft function following
kidney transplantation. Am J Transplant 6: 1639‑1645, 2006.
13. Nishida M, Kawakatsu H, Okumura Y and Hamaoka K: Serumand urinary neutrophil gelatinase‑associated lipocalin levels inchildren with chronic renal diseases. Pediatr Int 52: 563‑568,
2010.

EXPERIMENTAL AND THERAPEUTIC MEDICINE

14. Inoue H, Ohga S, Kusuda T, Kitajima J, Kinjo T, Ochiai M,
Takahata Y, Honjo S and Hara T: Serum neutrophil gela‑
tinase‑associated lipocalin as a predictor of the developmentof bronchopulmonary dysplasia in preterm infants. Early Hum
Dev 89: 425‑429, 2013.
15. Huynh TK, Bateman DA, Par ravicini E, Lorenz JM,
Nemerofsky SL, Sise ME, Bowman TM, Polesana E andBarasch JM: Reference values of urinary neutrophil gela‑
tinase‑associated lipocalin in very low birth weight infants.
Pediatr Res 66: 528‑532, 2009.
16. Gubhaju L, Sutherland MR, Horne RS, Medhurst A, Kent AL,
Ramsden A, Moore L, Singh G, Hoy WE and Black MJ:
Assessment of renal functional maturation and injury in preterm
neonates during the first month of life. Am J Physiol Renal
Physiol 307: F149‑F158, 2014.
17. Lavery AP, Meinzen‑Derr JK, Anderson E, Ma Q, Bennett MR,
Devarajan P and Schibler KR: Urinary NGAL in prematureinfants. Pediatr Res 64: 423‑428, 2008.
18. Roberts SB and Lucas A: Measurement of urinary constituentsand output using disposable napkins. Arch Dis Child 60:
1021‑1024, 1985.
19. Miall LS, Henderson MJ, Tur ner AJ, Brownlee KG,
Brocklebank JT, Newell SJ and Allgar VL: Plasma creatinine
rises dramatically in the first 48 hours of life in preterm infants.
Pediatrics 104: e76, 1999.
20. Karlowicz MG and Adelman RD: Nonoliguric and oliguric acuterenal failure in asphyxiated term neonates. Pediatr Nephrol 9:
718‑722, 1995.
21. Aggarwal A, Kumar P, Chowdhary G, Majumdar S and Narang A:
Evaluation of renal functions in asphyxiated newborns. J Trop
Pediatr 51: 295‑299, 2005.
22. Gupta BD, Sharma P, Bagla J, Parakh M and Soni JP: Renal
failure in asphyxiated neonates. Indian Pediatr 42: 928‑934,
2005.
23. Askenazi DJ, Montesanti A, Hunley H, Koralkar R, Pawar P,
Shuaib F, Liwo A, Devarajan P and Ambalavanan N: Urine
biomarkers predict acute kidney injury and mortality in very low
birth weight infants. J Pediatr 159: 907‑12.e1, 2011.
24. Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P,
Khandrika S, Mehta RL and Ambalavanan N: Baseline values ofcandidate urine acute kidney injury biomarkers vary by gesta‑
tional age in premature infants. Pediatr Res 70: 302‑306, 2011.
25. Parravicini E, Lorenz JM, Nemerofsky SL, O'Rourke M,
Barasch J and Bateman D: Reference range of urinary neutrophil
gelatinase‑associated lipocalin in very low‑birth‑weight infants:
Preliminary data. Am J Perinatol 26: 437‑440, 2009.
26. La Manna G, Galletti S, Capelli I, Vandini S, Nisi K, Aquilano G,
Mancini R, Carretta E, Montini G, Faldella G, et al: Urinary
neutrophil gelatinase‑associated lipocalin at birth predicts early
renal function in very low birth weight infants. Pediatr Res 70:
379‑383, 2011.
27. Parravicini E: The clinical utility of urinary neutrophil
gelatinase‑associated lipocalin in the neonatal ICU. Curr Opin
Pediatr 22: 146‑150, 2010.
28. Mori K and Nakao K: Neutrophil gelatinase‑associated lipocalinas the real‑time indicator of active kidney damage. Kidney Int 71:
967‑970, 2007.

5

29. Levey AS, Perrone RD and Madias NE: Serum creatinine andrenal function. Annu Rev Med 39: 465‑490, 1988.
30. Perrone RD, Madias NE and Levey AS: Serum creatinine as
an index of renal function: New insights into old concepts. Clin
Chem 38: 1933‑1953, 1992.
31. Schmidt‑Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ,
Devarajan P and Barasch J: Dual action of neutrophil gela‑
tinase‑associated lipocalin. J Am Soc Nephrol 18: 407‑413, 2007.
32. Gwira JA, Wei F, Ishibe S, Ueland JM, Barasch J and Cantley LG:
Expression of neutrophil gelatinase‑associated lipocalin
regulates epithelial morphogenesis in vitro. J Biol Chem 280:
7875‑7882, 2005.
33. Parravicini E, Nemerofsky SL, Michelson KA, Huynh TK,
Sise ME, Bateman DA, Lorenz JM and Barasch JM: Urinary
neutrophil gelatinase‑associated lipocalin is a promisingbiomarker for late onset culture‑positive sepsis in very low birthweight infants. Pediatr Res 67: 636‑640, 2010.
34. Lao TT, Loong EP, Chin RK and Lam YM: Renal function in the
newborn. Newborn creatinine related to birth weight, maturity
and maternal creatinine. Gynecol Obstet Invest 28: 70‑72, 1989.
35. Filler G, Guerrero‑Kanan R and Alvarez‑Elías AC: Assessmentof glomerular filtration rate in the neonate: Is creatinine the best
tool? Curr Opin Pediatr 28: 173‑179, 2016.
36. Filler G, Lopes L and Awuku M: The Importance of Accurately
Assessing Renal Function in the Neonate and Infant. Adv Clin
Chem 71: 141‑156, 2015.
37. Wu J, Ding Y, Zhu C, Shao X, Xie X, Lu K and Wang R: Urinary
TNF‑ α and NGAL are correlated with the progression ofnephropathy in patients with type 2 diabetes. Exp Ther Med 6:
1482‑1488, 2013.
38. Du Y, Hou L, Guo J, Sun T, Wang X and Wu Y: Renal
neutrophil gelatinase‑associated lipocalin and kidney injury
molecule‑1 expression in children with acute kidney injury
and Henoch‑Schönlein purpura nephritis. Exp Ther Med 7:
1130‑1134, 2014.
39. Wu BL, Li CQ, Du ZP, Zhou F, Xie JJ, Luo LW, Wu JY,
Zhang PX, Xu LY and Li EM: Functional analysis of the mRNA
profile of neutrophil gelatinase associated lipocalin overex‑pression in esophageal squamous cell carcinoma using multiple
bioinformatic tools. Mol Med Rep 10: 1800‑1812, 2014.
40. Zhang P, Li Y, Zhang LD, Wang LH, Wang X, He C and Lin ZF:
Proteome changes in mesenteric lymph induced by sepsis. Mol
Med Rep 10: 2793‑2804, 2014.
41. Olguner CG, Koca U, Altekin E, Ergür BU, Duru S, Girgin P,Taşdöğen A, Gündüz K, Güzeldağ S, Akkuş M, et al: Ischemic
preconditioning attenuates lipid peroxidation and apoptosis in
the cecal ligation and puncture model of sepsis. Exp Ther Med 5:
1581‑1588, 2013.
42. Zhang PX, Zhang FR, Xie JJ, Tao LH, Lü Z, Xu XE, Shen J,
Xu LY and Li EM: Expression of NGAL and NGALR in humanembryonic, fetal and normal adult tissues. Mol Med Rep 6:
716‑722, 2012.
43. Kesik V, Demirkaya E and Buyukpamukçu M: Urinary neutrophil
gelatinase associated lipocalin as a biomarker in ifosfamide
induced chronic renal failure. Eur Rev Med Pharmacol Sci 19:
4851‑4857, 2015.