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Urinary NGAL and KIM-1 Are the Early Detecting Biomarkers of Preterm Infants with Acute Kidney Injury

  • Siddhi Memorial Hospital (for Women and Children)
Yangtze Medicine, 2019, 3, 183-194
ISSN Online: 2475-7349
ISSN Print: 2475-7330
10.4236/ym.2019.33019 Jun. 28, 2019 183 Yangtze
Urinary NGAL and KIM-1 Are the Early
Detecting Biomarkers of Preterm Infants with
Acute Kidney Injury
Hongzhu Lu1,2, Qihong Fan1,2, Lu Wang1, Nipun Shrestha1, Sijan Thapa1
1Department of Pediatrics, The First Clinical College, Yangtze University, Jingzhou, China
2Pediatric Research Institute of Yangtze University, Jingzhou, China
: Acute kidney injury (AKI) is common in neonates. However,
early diagnosis is difficult. Different biomarkers for early diagnosis of AKI,
such as NGAL, KIM-1, Cys-C, IL-18,
2-microglobulin have been proposed.
But regarding premature infant, there is very little research that has been re-
: To investigate the role of urinary NGAL and Kim-1 bio-
markers for early diagnosis of AKI in premature neonates.
cases were divided into experimental group (60 cases) and controls group (20
cases). Of 60 cases,
24 patients met the criteria for AKI group; the remaining
36 were non-AKI group. Blood and urine samples, 1 ml each, were
from all subjects at first day, second day, third day and seventh day of life.
Urine NGAL and KIM-1 were measured by ELISA.
Results: The urinary
NGAL and KIM-1 are significantly higher in AKI group than Non-A
KI group
and normal control group in the first three days. They present earlier than
classical Scr.
Urinay NGAL and Kim-1 are beneficial
for the early diagnosis of AKI in preterm neonates.
Neonate, Acute Kidney Injury, NGAL, KIM-1
1. Introduction
Acute Kidney Injury (AKI), formerly known as Acute Renal Failure (ARF), is
one of the numbers of conditions that affect kidney function and structure. AKI
is currently defined as reduction in kidney function, including decreased glo-
merular filtration rate (GFR) and kidney failure. The change in serum creatinine
How to cite this paper:
Lu, H.Z.,
Wang, L., Shrestha, N. and Thapa, S.
9) Urinary NGAL and KIM-
1 Are the
Early Detecting Biomarkers of Preterm
Infants with Acute Kidney Injury
, 183-194.
December 20, 2018
June 25, 2019
June 28, 2019
Copyright © 201
9 by author(s) and
Research Publishing Inc.
This work is licensed under the Creative
Commons Attribution International
License (CC BY
Open Access
H. Z. Lu et al.
10.4236/ym.2019.33019 184
Yangtze Medicine
(SCr) and urine output are the classical parameter used to diagnose severity and
stage of AKI. The RIFLE criteria have been proposed by the Acute Dialysis
Quality Initiative (ADQI) group, aid in the staging of patients with AKI [1] [2].
According to World Health Organization statistics, 28% of all neonatal deaths
are due to premature birth. In the past 20 years, some developed countries have
preterm birth rates ranging from 5% to 7% [3]. In recent years, a series of studies
have found that mortality of preterm infants is closely related to preterm infants
with renal impairment [4] [5]. Premature infants are at unique risk for develop-
ing AKI due to incomplete nephrogenesis, early exposure to nephrotoxic medi-
cations (
Indomethacin, Ibuprofen, cefotaxime, aminoglycosides), and coex-
isting conditions such as patent ductus arteriosus (PDA) and respiratory distress
syndrome (RDS). AKI prevention and therapy have as of yet been rather unsuc-
cessful and unsatisfactory [6] [7]. Serum creatinine concentrations are influ-
enced by many factors. A significant disadvantage of these tests is the time delay
between injury and detection, making the tests insensitive and unreliable for di-
agnostic and prognostic measurements [6]. It is suggested to use other markers
which are stable over time and are not affected by muscle mass or tubular reab-
sorption and secretion. Specific proteins excreted in the urine after injury to par-
ticular segments of the nephron can serve as biomarkers for assessing the site
and severity of renal damage [7]. Currently, for adults and children, many ex-
perts and scholars have proposed different biomarkers for early diagnosis of AKI
[8], such as NGAL, KIM-1, Cys-C, etc. But regarding premature infant, there is
very little research that has been reported. NGAL is a 25-kDa protein that be-
longs to lipocalin group which is highly expressed in proximal tubular epithelial
cells and has role in renal tubular epithelial cells formation and repair. It is ex-
pressed in neutrophils and in low levels in the kidney, prostate, and epithelia of
the respiratory and alimentary tracts [9] [10]. When AKI occurs, tubular epi-
thelial cell is damaged and blood and urine NGAL are abundantly expressed
[11]. KIM-1 belongs to immunoglobulin super family. It is a type 1transmembrane
glycoprotein, the mucin, immunoglobulins composition, an adhesion molecule
[12]. We investigate the role of urinary NGAL and Kim-1 biomarkers for early
diagnosis of AKI in premature neonates.
2. Materials and Methods
2.1. Patients
Eighty cases were divided into experimental group (60 cases, gastational age less
than 34 weeks) and controls group (20 cases, gastational age more than 37
weeks), excluding infection, congenital malformation of the urinary system, cas-
es of medication during pregnancy by the mother. The control group was with-
out risk factors like abnormal pregnancy or use of nephrotoxic medication or
trauma, asphyxia, congenital uninary tract malformation. Families of preterm
infants involved in all the cases were informed about the study and the consent
was signed. The approval of the hospital ethics committee was obtained. Record
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of all selected cases infants and their mother was maintained like inpatient
number, name, sex, gestational age, birth weight, Apgar scores, gravidity and
parity. Case-control data analysis was performed.
Of the 80 cases, 60 cases were the experimental group and 20 cases were the
control group, according to the diagnostic criteria for acute kidney injury in
2007 the United States AKIN (within 48 hours, SCr increased to more than 26.5
μmol/L; or percentage increase in SCr by more than or equal to 50%; or reduc-
tion in urine output less than 0.5 ml/kg/hour over six hours), the experimental
group was divided into AKI group, the non-AKI group. Out of 60 cases, 24 pa-
tients met the criteria for AKI group; the remaining 36 were non-AKI group; the
other 20 cases without any other risk factors were full-term newborns grouped
as normal controls.
Blood and urine samples, 1 ml each, was collected from all subjects at first
day, second day, third day and seventh day of life. The samples were immediate-
ly centrifuged (room temperature 18˚C, 3500 rpm, 5 min), (low speed automatic
balance centrifuge, LDE5-2, Beijing, China). After centrifugation, the superna-
tant (serum) 100 μl was kept in hospital central laboratory at −80˚C tempera-
ture. Blood samples were collected by conventional tube, urine specimens were
collected in urine tube.
2.2. Detection of Samples
Nissan OLYMPUS AU5400 automatic biochemical analyzer available in our
hospital laboratory was used for serum creatinine.
Urine NGAL and KIM-1 were measured by enzyme-linked immunosorbent
assay (ELISA), the kit provided by Shanghai Biological Technology Co., Ltd.
(SEB388Hu 96T). The procedure was followed strictly according to the kit in-
2.3. Statistical Analysis
Measurement data were expressed as mean ± standard deviation. The compari-
son between the groups was done using the F test. Correlation between the index
and serum creatinine were evaluated using linear regression. Each index sensi-
tivity and specificity was evaluated with the area under the ROC curve. Statistical
analysis was done using SPSS19.0.
3. Results
3.1. Eighty Neonates Was Enrolled
We investigated gestational ages, birth weight, and Apgar score of all cases. The
summary clinical data of all neonates is illustrated in Table 1.
3.2. AKI Group, the Non-AKI Group, Control Group of Preterm
Infants of Different Age and Scr
From Table 2, Figure 1, it is seen that for the same-day-old premature children,
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Figure 1. Changes of Scr in premature infants with different age groups.
Table 1. 80 cases of neonatal clinical data.
Clinical data Number of cases
Gender Male/Female 42/38
Gestational Age
≤34 Week 18
34 - 36 Week 42
≥37 Week 20
Birth Weight
≤1.5 kg 7
1.5 kg - 2 kg (Including 2 kg) 17
2 kg - 3 kg (Including 3 kg) 39
>3 kg 24
Apgar 1 minute
0 - 3 Score (Including 3 score) 1
4 - 7 Score (Including 7 score) 13
>7 Score 66
Mode of Delivery
Birth 13
Caesarean section 67
Table 2. Changes in Scr in preterm infants of different age groups (μmol/L) (
± S).
n Day 1 Day 2 Day 3 Day 7
AKI Group 26 52.5 ± 30.3 56.2 ± 27.5 98.4 ± 36.1 65.3 ± 27.5
Non AKI Group 34 46.0 ± 9.4 47.1 ± 10.2 57.3 ± 18.5 42.2 ± 14.3
Normal control group 20 39.1 ± 8.1 37.8 ± 7.4 36.5 ± 8.3 38.7 ± 8.8
F value 2.869 6.319 4.292 15.109
P value 0.063 0.003 <0.001 <0.001
compare P value 0.186 0.052 <0.001 <0.001
compare P value 0.019 0.001 <0.001 <0.001
compare P value 0.201 0.061 0.003 0.512
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Scr is significantly high in AKI group compared to control group. This differ-
ence is statically significant. It is seen that in AKI and control group, for Scr at
day 1, 2, 3 and 7, P < 0.05 and the difference is statically significant. For the
Same-day-old premature children on the first day and second day, P > 0.05 in
AKI and non-AKI groups, the difference is not statistically significant. At 3rd
day and 7th day, P < 0.05 in AKI group and non-AKI group comparison, the
difference is statistically significant. Comparing Non-AKI group and normal
control, first 1, 2, 7 days P > 0.05, the first three days P < 0.05.
In the AKI group, there is no significant change in Scr in first and second day
and then increases with increasing age and again decreases by seventh day. In
case of Non-AKI group, each time the reading is slightly higher than those in the
control group, the first decline is seen in seventh days. In the control group,
from day 1 to day 7, Scr is basically unchanged.
3.3. Changes of NGAL in Preterm Children of Different Age Group
in AKI Group, the Non-AKI Group and Control Group
Table 3 and Figure 2 show that NGAL is significantly high in AKI group and
Non-AKI group when compared to control group of the preterm child of same
age. This difference is statistically significant. AKI group and non-AKI group, on
days 1 to 3, P < 0.05 difference was statistically significant. AKI group and the
normal control group, at day 1, 2, 3, 7 days, P < 0.05 and the difference was sta-
tistically significant. Non-AKI group and normal control group, who was born
the first 1, 2, 3, 7 days, P < 0.05 difference was again statistically significant. For
AKI group and non-AKI group preterm children, NGAL increased with age.
NGAL was on rise during the first three days and the first decline was seen
slightly on the seventh day. AKI group compared with non-AKI group and
normal control group, the first day there is a clear upward rise on the first two
days, significantly increased on the first three days and decreased on seventh
Table 3. Changes in NGAL in preterm children of different age group (ng/ml) (
± S).
N Day 1 Day 2 Day 3 Day 7
AKI Group 26 2.1 ± 1.4 2.23 ± 1.49 2.58 ± 1.51 1.48 ± 1.33
Non AKI Group 34 1.72 ± 1.19 1.81 ± 1.37 1.87 ± 1.38 1.44 ± 1.17
Control 20 0.54 ± 0.28 0.66 ± 0.45 0.83 ± 0.90 0.67 ± 0.60
F value 11.494 9.302 9.892 3.731
P value <0.001 <0.001 <0.001 0.028
compare P 0.039 0.041 0.042 0.035
compare P <0.001 <0.001 <0.001 0.017
compare P <0.001 0.002 0.007 0.016
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Figure 2. Changes of NGAL in preterm at different ages.
3.4. KIM-1 in AKI Group, Non-AKI Group, Control Group of
Preterm Infants Different Ages
Table 4 and Figure 3 show that KIM-1 is significantly high in AKI group and
Non-AKI group when compared to control group of the preterm child of same
age. This difference is statistically significant. AKI group and non-AKI group, on
days 1 to 7, P < 0.05 difference was statistically significant. AKI group and the
normal control group, at day 1, 2, 3, 7 days, P < 0.05 and the difference was sta-
tistically significant. Non-AKI group and normal control group, was born the
first 1, 2, 3, 7 days, P > 0.05 difference was statistically not significant.
For AKI group and non-AKI group preterm children, KIM-1 increased with
age. KIM-1 was on rise during the first three days and then decline was seen
slightly on the seventh day. AKI group compared with non-AKI group and
normal control group, the first day there is a clear upward rise on the first two
days, significantly increased on the first three days and decreased on seventh
4. Discussion
The potential role of urine protein biomarkers to detect kidney damage are an
area of active investigation. The present study showed that the urinary NGAL
and KIM-1 are significantly higher in AKI group than Non-AKI group and
normal control group in the first three days. They present earlier than classical
Scr. So the urinay NGAL and Kim-1 are benifical biomarkers for the early diag-
nosis of AKI in preterm neonates.
In the case of AKI, NGAL is secreted in high levels into the blood and urine
within 2 hours of injury [13]. Urinary NGAL appears to be the most promising
AKI biomarker and it is the most strikingly upregulated gene and overexpressed
protein in the kidney after ischemia [14].
The NGAL level measured in an individual is proportional to the severity of
the AKI [15]. Renal expression of NGAL increases in the kidneys after injury for
a variety of reasons. Many studies have evaluated urinary and serum NGAL
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Figure 3. Changes of KIM-1 in premature infants of different age groups.
Table 4. Preterm children of different age groups and KIM-1 (ng/ml) (
± S).
n Day 1 Day 2 Day 3 Day 7
AKI Group 26 574.1 ± 562.1 583 ± 896.4 807.3 ± 1344 592.5 ± 806.2
Non AKI Group 34 276 ± 306 299 ± 328.2 473.9 ± 688.4 265.4 ± 294.3
Control 20 95.96 ± 59.17 106.2 ± 80.9 114.0 ± 69.5 143.6 ± 106.6
F value 9.553 4.346 3.445 5.216
P value <0.001 0.016 0.037 0.008
compare P 0.003 0.045 0.048 0.014
Compare P <0.001 0.005 0.011 0.004
Compare P 0.096 0.221 0.155 0.391
capacity to predict AKI in both adults [16] [17] and older children [18] [19].
NGAL in children and newborn range has been relatively a widespread concern.
A study on children with pediatric cardiopulmonary bypass operations showed
that urinary NGAL concentrations above 50 ng/mL in 2 hours after surgery and
serum creatinine levels 50% over basal values. Normally, children tend to have
almost undetectable levels of NGAL [20]. Hundreds of clinical studies demon-
strate that NGAL measures kidney injury but the studies are mainly done in
adult population and very few studies were done in pediatric population. Lavery
et al.
[21] studied 20 children with low birth weight, weighing from 500 g to
1500 g and collected their urine for first 2 week of life and concluded that urine
NGAL can be easily obtained in premature infants. Specifically in the neonatal
population, serum and urine NGAL were evaluated in patients after Cardiopul-
monary Bypass (CPB) surgery [20]. Plasma and serum NGAL collected 2 hours
after CPB were able to predict AKI with a sensitivity and specificity of nearly
90%. Another study evaluated urinary NGAL at day 1 in preterm infants and af-
ter full adjustment for other factors; it remained significantly associated with
AKI development [22]. A recent study on AKI in preterm infants concluded that
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urinary NGAL may be very useful to predict AKI development prior to changes
in serum creatinine in preterm infants [23]. The study found that NGAL level
was much higher in AKI group than in non-AKI group. In non-AKI group, the
level of NGAL in control group was 0.598 µg/ml whereas in AKI group it was
found to be as high as 4.24 µg/ml. This study was performed on preterm infants
below 32 weeks of gestation age. Oncel NY
et al.
[24] studied 41 cases of new-
born with a diagnosis of perinatal asphyxia and classified the cases into AKI and
non-AKI groups. The AKI group included 15 newborns and Non-AKI group in-
cluded 26 newborns. The biomarker NGAL was measured on day 1 and day 4.
The study concluded that urinary NGAL was higher in patients with AKI on day
as well as day 4 and it can be used as an important diagnostic biomarker in such
patients. Our results showed the same significance with the above.
KIM-1, under normal physiological conditions, did not increase or increase in
low amount but expression was significantly increased in ischemic or nephro-
toxic injury [25] [26]. The KIM-1 is stable in the urine for prolonged periods of
time and can be detected in the kidney and urine in a number of nephrotoxic
models in animals [27] [28] and in humans with AKI [29]. During proximal tu-
bular damage KIM-1 can be detected in urine, in the form of a soluble fragment,
stable nature [30] [31]. Han
et al.
demonstrated marked expression of KIM-1 in
kidney biopsy specimens from six patients with acute tubular necrosis, and
found elevated urinary levels of KIM-1 after an initial ischemic renal insult,
prior to the appearance of casts in the urine [12]. A longitudinal prospective
study conducted by van Timmeren
et al.
[32] reported that elevated urinary
KIM-1 serves as an independent predictor of long-term graft loss in renal trans-
plant recipients (n = 145 patients) independent of donor age, creatinine clear-
ance and proteinuria.
Sabbisetti VS
et al.
[33], conducted a study on ischemia reperfusion in mice
and found that there are significant expression of KIM-1 for 12 hours before Scr
increased. Sprenkle P
et al.
[34] found that, in the event of tissue ischemia, by
detecting Scr alone prediction of early AKI was missed. The KIM-1 has a value
of early diagnosis. Mihye Jeong
et al.
[35], studied drug-induced renal toxicity in
rats and found that KIM-1 has important significance in early detection of AKI
with high sensitivity. Song L
et al.
[36], studied on 69 patients after renal trans-
plantation and found that increasing the tubular cell damage and the extent of
renal injury and KIM-1 levels were positively correlated. Van Timmeren MM
[37] studied in 109 cases with biopsy specimens, of which 102 cases have kid-
ney injury and seven cases of normal controls. Urinary KIM-1 was measured by
ELISA, the study found that KIM-1 was highly expressed in proximal tubules.
KIM-1 can be used as non-invasive biomarker of kidney injury. Tubular KIM-1
levels are virtually undetectable in healthy kidney tissues but are markedly in-
creased after injury to the kidney [12]. Lee HE
et al.
[38], demonstrated signi-
ficance expression of KIM-1 on cohort study of infants with febrile urinary tract
infection that suggest renal injujry.
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Zwiers AJ
et al.
[39] conducted a prospective observational cohort study of
100 term-born infants ages 1 day to 1 year on mechanical ventilation. Thirty-five
patients had evidence of AKI within the first 48 hours post-admission, of whom
24 (69%) already had AKI when they entered the PICU. KIM-1 concentrations
in AKI peaked between 6 to 12 hours and between 12 to 24 hours post-admission.
Gurkan Genc
et al.
[40] studied in 48 premature babies hospitalized in the neo-
natal intensive care unit were included in the study and divided into three
groups: group I, healthy premature infants; group II, preterm infants with RDS
without AKI; group III, preterm infants with RDS and AKI. Urinary KIM-1
along with Scr levels were measured with ELISA on days 1, 3, and 7 of life. On
day 1 babies with RDS and AKI, KIM-1 were higher than the other two groups.
Nephrotoxicity is a common side effect of therapeutic interventions, environ-
mental insults, and exposure to toxicants. Although biomarkers for nephrotoxic-
ity are available, they often lack sensitivity and are not specific as indicators of
epithelial cell injury [41] [42]. Urinary KIM-1 expression may be detected after
exposure to a variety of nephrotoxic agents, even when serum creatinine con-
centrations do not increase, and this has been accepted by regulatory authorities
as a sensitive biomarker of AKI [43]. We also found that urinary KIM-1is a very
sensitive biomarker in neonates with AKI.
Our study results indicated that both NGAL and KIM-1 are more sensitive
and easier to detect for the neonates with AKI than Scr.
5. Conclusion
AKI is vital for the neonates, especially preterm neonates. Early diagnosis is crit-
ical for the treatment and better prognosis. Our study showed that urinay NGAL
and KIM-1 are beneficial and easier biomarkers for the early diagnosis of AKI in
preterm neonates. However, further investigation that whether these biomarkers
can predict the clinical outcome is indicated. Larger samples of preterm neo-
nates with different courses of AKI are needed.
Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this
[1] Bellomo, R., Ronco, C., Kellum, J.A.,
et al.
(2004) Acute Renal FailureDefinition,
Outcome Measures, Animal Models, Fluid Therapy and Information Technology
Needs: The Second International Consensus Conference of the Acute Dialysis Qual-
ity Initiative (ADQI) Group.
Critical Care
, 8, R204-R212.
[2] Lameire, N., Van Biesen, W. and Vanholder, R. (2005) Acute Renal Failure.
, 365, 417-430.
[3] Beck, S., Wojdyla, D., Say, L.,
et al.
(2010) The Worldwide Incidence of Preterm
Birth: A Systematic Review of Maternal Mortality and Morbidity.
Bulletin of the
World Health Organization
, 88, 31-38.
H. Z. Lu et al.
10.4236/ym.2019.33019 192
Yangtze Medicine
[4] Walker, M.W., Clark, R.H. and Spitzer, A.R. (2011) Elevation in Plasma Creatinine
and Renal Failure in Premature Neonates without Major Anomalies: Terminology,
Occurrence and Factors Associated with Increased Risk.
Journal of Perinatology
31, 199-205.
[5] Csaicsich, D., Russo-Schlaff, N., Messerschmidt, A., Weninger, M., Pollak, A. and
Aufricht, C.
(2008) Renal Failure, Comorbidity and Mortality in Preterm Infants.
Wiener Klinische Wochenschrift
, 120, 153-157.
[6] Sweetman, D.U. (2017) Neonatal Acute Kidney InjurySeverity and Recovery Pre-
diction and the Role of Serum and Urinary Biomarkers.
Early Human Develop-
, 105, 57-61.
[7] Harrill, A.H., Lin, H., Tobacyk, J. and Seely, J.C
(2018) Mouse Population-Based
Evaluation of Urinary Protein and miRNA Biomarker Performance Associated with
Cisplatin Renal Injury.
Experimental Biology and Medicine
, 243, 237-247.
[8] Askenazi, D.J., Koralkar, R., Letivan, E.B.,
et al.
(2011) Baseline Values of Candidate
Urine Acute Kidney Injury (AKI) Biomarkers Vary by Gestational Age in Prema-
ture Infants.
Pediatric Research
, 70, 302-306.
[9] Cowland, J.B. and Borregaard, N. (1997) Molecular Characterization and Pattern of
Tissue Expression of the Gene for Neutrophil Gelatinase-Associated Lipocalin from
, 45, 17-23.
[10] Friedl, A., Stoesz, S.P., Buckley, P. and Gould, M.N. (1999) Neutrophil Gelati-
nase-Associated Lipocalin in Normal and Neoplastic Human Tissues. Cell
Type-Specific Pattern of Expression.
The Histochemical Journal
, 31, 433-441.
[11] Dagher, P.C., Herget-Rosenthal, S., Ruehm, S.G., Jo, S.-K., Star, R.A.,
et al.
Newly Developed Techniques to Study and Diagnose Acute Renal Failure.
of the American Society of Nephrology
, 14, 2188-2198.
[12] Han, W.K., Bailly, V., Abichandani, R.,
et al.
(2002) A Novel Biomarker for Human
Renal Proximal Tubule Injury.
Kidney International
, 62, 237-244.
[13] Bennett, M., Dent, C.L., Ma, Q.,
et al.
(2008) Urine NGAL Predicts Severity of Acute
Kidney Injury after Cardiac Surgery: A Prospective Study.
Clinical Journal of the
American Society of Nephrology
, 3, 665-673.
[14] Mishra, J., Qing, M.N., Prada, A., Mitsnefes, M., Zahedi, K.,
et al.
(2003) Identifica-
tion of Neutrophil Gelatinase-Associated Lipocalin as a Novel Early Urinary Bio-
marker for Ischemic Renal Injury.
Journal of the American Society of Nephrology
14, 2534-2543.
[15] Haase, M., Devarajan, P., Haase-Fielitz, A.,
et al.
(2011) The Outcome of Neutrophil
Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury: A Multi-
center Pooled Analysis of Prospective Studies.
Journal of the American College of
, 57, 1752-1761.
[16] Lippi, G., Aloe, R., Storelli, A., Cervellin, G. and Trenti, T.
(2012) Evaluation of
NGAL Test, a Fully-Automated Neutrophil Gelatinase-Associated Lipocalin
(NGAL) Immunoassay on Beckman Coulter AU 5822.
Clinical Chemistry and La-
boratory Medicine
, 50, 1581-1584.
[17] Wagener, G., Gubitosa, G., Wang, S., Borregaard, N., Kim, M. and Lee, H.T. (2008)
H. Z. Lu et al.
10.4236/ym.2019.33019 193
Yangtze Medicine
Urinary Neutrophil Gelatinase Associated Lipocalin and Acute Kidney Injury after
Cardiac Surgery.
American Journal of Kidney Diseases
, 52, 425-433.
[18] Di Grande, A., Giuffrida, C., Carpinteri, G.,
et al.
(2009) Neutrophil Gelati-
nase-Associated Lipocalin: A Novel Biomarker for the Early Diagnosis of Acute
Kidney Injury in the Emergency Department.
European Review for Medical and
Pharmacological Sciences
, 13, 197-200.
[19] Parikh, C.R., Devarajan, P., Zappitelli, M.,
et al.
(2011) Postoperative Biomarkers
Predict Acute Kidney Injury and Poor Outcomes after Pediatric Cardiac Surgery.
Journal of the American Society of Nephrology
, 22, 1737-1747.
[20] Krawczeski, C.D., Woo, J.G., Wang, Y., Bennett, M.R., Ma, Q. and Devarajan, P.
(2011) Neutrophil Gelatinase-Associated Lipocalin Concentrations Predict Devel-
opment of Acute Kidney Injury in Neonates and Children after Cardiopulmonary
The Journal of Pediatrics
, 158, 1009-1015.
[21] Lavery, A.P., Meinzen-Derr, J.K., Anderson, E.,
et al.
(2008) Urinary NGAL in Pre-
mature Infants.
Pediatric Research
, 64, 423-428.
[22] Tabel, Y., Elmas, A., Ipek, S., Karadag, A., Elmas, O. and Ozyalin, F.
(2014) Urinary
Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker for Prediction of
Acute Kidney Injury in Preterm Infants.
American Journal of Perinatology
, 31,
[23] Hanna, M., Brophy, P.D., Giannone, P.J.,
et al.
(2016) Early Urinary Biomarkers of
Acute Kidney Injury in Preterm Infants.
Pediatric Research
, 80, 218-223.
[24] Oncel, M.Y., Canpolat, F.E., Arayici, S., Joshi, M.S., Bauer, J.A. and Rao, S.R.
Urinary Markers of Acute Kidney Injury in Newborns with Perinatal Asphyxia.
Renal Failure
, 38, 882-888.
[25] Cruz, D.N., Goh, C.Y., Haase-Fielitz, A., Ronco, C. and Haase, M. (2010) Early
Biomarkers of Renal Injury.
Congestive Heart Failure
, 16, 25-31.
[26] Dieterich, C., Puey, A., Lin, S.,
et al.
(2009) Gene Expression an Alysis Reveals New
Possible Mechanisms of Vancomycin Induced Nephrotoxicity and Identifies Gene
Markers Candidates.
Toxicological Sciences
, 107, 258-269.
[27] Amin, R.P., Vickers, A.E., Sistare, F.,
et al.
(2004) Identification of Putative Gene
Based Markers of Renal Toxicity.
Environmental Health Perspectives
, 12, 465-479.
[28] Ichimura, T., Hung, C.C., Yang, S.A.,
et al.
(2004) Kidney Injury Molecule-1: A
Tissue and Urinary Biomarker for Nephrotoxicant-Induced Renal Injury.
Journal of Physiology
Renal Physiology
, 286, F552-F563.
[29] Han, W.K. and Bonventre, J.V. (2004) Biologic Markers for the Early Detection of
Acute Kidney Injury.
Current Opinion in Critical Care
, 10, 476-482.
[30] Zhang, P.L., Rothblum, L.I., Han, W.K., Blasick, T.M., Potdar, S. and Bonventre,
J.V. (2008) Kidney Injury Molecule-1 Expression in Transplant Biopsies Is a Sensi-
tive Measure of Cell Injury.
Kidney International
, 73, 608-614.
H. Z. Lu et al.
10.4236/ym.2019.33019 194
Yangtze Medicine
[31] Vaidya, V.S., Ramirez, V., Ichimura, T.,
et al.
(2006) Urinary Kidney Injury Mole-
cule-1: A Sensitive Quantitative Biomarker for Early Detection of Kidney Tubular
American Journal of Physiology
Renal Physiology
, 290, 517-529.
[32] Van Timmeren, M.M., Vaidya, V.S., van Ree, R.M.,
et al.
(2007) High Urinary Ex-
cretion of Kidney Injury Molecule-1 Is an Independent Predictor of Graft Loss in
Renal Transplant Recipients.
, 84, 1625-1630.
[33] Sabbisetti, V.S., Ito, K., Wang, C., Yang, L., Mefferd, S.C. and Bonventre, J.V. (2013)
Novel Assays for Detection of Urinary KIM-1 in Mouse Models of Kidney Injury.
Toxicological Sciences
, 131, 13-25.
[34] Sprenkle, P. and Russo, P. (2013) Molecular Markers for Ischemia, Do We Have
Something Better than Creatinine and Glomerular Filtration Rate.
Archivos Es-
pañoles de Urología
, 66, 99-114.
[35] Jeong, M., Kim, Y.W., Min, J.R.,
et al.
(2013) Kidney Toxicity Induced by 13 Weeks
Exposure to the Fruiting Body of
Paecilomyces sinclairii
in Rats.
Toxicological Re-
, 28, 179-185.
[36] Song, L., Xue, L., Yu, J.,
et al.
(2013) Kidney Injury Molecule-1 Expression Is Closely
Associated with Renal Allograft Damage.
Bosnian Journal of Basic Medical
, 13, 170-174.
[37] Van Timmeren, M.M., Van den Heuvel, M.C., Bailly, V.,
et al.
(2007) Tubular Kid-
ney Injury Molecule-1 (KIM-1) in Human Renal Disease.
The Journal of Pathology
212, 209-217.
[38] Lee, H.E., Kim do, K., Kang, H.K. and Park, K. (2015) The Diagnosis of Febrile
Urinary Tract Infection in Children May Be Facilitated by URINARY Biomarkers.
Pediatric Nephrology
, 30, 123-130.
[39] Zwiers, A.J., de Wildt, S.N., van Rosmalen, J.,
et al.
(2015) Urinary Neutrophil Gela-
tinase-Associated Lipocalin Identifies Critically Ill Young Children with Acute
Kidney Injury Following Intensive Care Admission: A Prospective Cohort Study.
Critical Care
, 19, 181.
[40] Genc, G., Ozkaya, O., Avci, B.,
et al.
(2004) Kidney Injury Molecule-1 as a Promis-
ing Biomarker for Acute Kidney Injury in Premature Babies.
American Journal of
Renal Physiology
, 286, F552-F563.
[41] Muramatsu, Y., Tsujie, M., Kohda, Y.,
et al.
(2002) Early Detection of Cysteine Rich
Protein 61 (CYR61, CCN1) in Urine Following Renal Ischemic Reperfusion Injury.
Kidney International
, 62, 1601-1610.
[42] Price, R.G. (2000) Urinalysis to Exclude and Monitor Nephrotoxicity.
Clinica Chi-
mica Acta
, 297, 173-182.
[43] Waring, W.S. and Moonie, A. (2011) Earlier Recognition of Nephrotoxicity Using
Novel Biomarkers of Acute Kidney Injury.
Clinical Toxicology
, 49, 720-728.
... A significant rise in serum creatinine is seen only after 48 to 72 hours of renal insult and is detected when more than 50% of the glomerular filtration rate (GFR) is lost [18]. e new biomarkers such as neutrophil gelatinase lipoprotein (NGAL), cystatin C (CysC), and kidney injury molecule-1 (KIM-1) are beneficial in early detection of AKI in neonates, including premature babies [18,19]. However, there are limited studies regarding these new biomarkers in neonates and they may not be available in resource-limited regions. ...
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Staphylococcus toxic shock syndrome (TSS) is not well described in neonates. The present criteria for diagnosis of TSS have not yet been validated in neonates. Here, we present a case of a 13-day-old female baby who presented with acute kidney injury (AKI). She had a pus-draining lesion on the head, and the pus grew Staphylococcus aureus. Based on the clinical criteria of fever, desquamation, hypotension, and AKI and laboratory criteria of absence of growth of any organisms in blood and cerebrospinal fluid, we diagnosed the case as TSS. She was treated with antibiotics, oxygen, and fluids, along with inotropic support and mechanical ventilation, and she recovered fully and was discharged on day 17 of admission. As there is no single test to diagnose TSS and it is uncommon in neonates, physicians should be familiar with the clinical presentation of the disease to make early diagnosis.
... Since glomeruli filter plasma NGAL freely, a decrease in glomerular filtration due to renal pathology causes NGAL to accumulate in the systemic circulation [11]. ...
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DETERMINATION OF THE DEGREE OF THE KIDNEY INJURY IN LOW BIRTH WEIGHT INFANTS DEPENDING ON THE CORRESPONDENCE OF THEIR ANTHROPOMETRIC PARAMETERS TO GESTATIONAL AGE Akhundova A. A. Abstract. Aim. Using novel biomarkers of kidney damage, to compare the functional state of kidneys in SGA and AGA newborns with ischemic nephropathy (IN). Materials and Methods. A total of 72 newborns were included in the study. SGA (small for gestational age) new- borns comprised 33, while AGA (appropriate for gestational age) newborns comprised 39 of the total number of infants. They were split into three groups based on the intensity of their IN (children with IN of I, II, or III degrees), with each group divided into two subgroups. On days 1-3 and 7-10 of the patient’s life, blood and urine samples were taken to determine the levels of KIM-1 and NGAL in the urine, as well as Cystatin C in the blood serum. The levels of biomarkers were determined by the enzyme-linked immunosorbent assay (ELISA). Results. The difference in creatinine levels between the subgroups on days 1-3 and 7-10 was significant only in the II degree of nephropathy. In both the I and II degrees of nephropathy, the values of KIM-1 in SGA newborns sub- stantially exceeded the values of this marker in the AGA subgroup. The highest concentrations of KIM-1 were found in the subgroups of III degree IN, with nearly equal values. The subgroup with SGA newborns had slightly higher levels of NGAL in the urine on days 1-3 with II degree IN and days 7-10 with III degree of IN. Statistically significant Cystatin C values were found in newborns with developmental delays on the 1st-3rd days of life and on the 7th-10th days of life. Disscusion. Thus, relative to premature infants with a weight that corresponds to their gestational age, the tubular apparatus of the kidneys in newborns with intrauterine growth retardation is more vulnerable. High KIM-1 values, indicate the severity of tubular disorders in SGA newborns at the I degree of IN. Despite the lack of a statisti- cally significant difference in creatinine levels between subgroups with III degrees of IN, the level of NGAL in infants who had a developmental delay was statistically significantly higher than in AGA newborns, indicating that this category of newborns may develop the terminal stage of AKI.A rise in Cystatin C concentration indicates that the res- toration of glomerular filtration has been disrupted, despite the glomerular apparatus’s anatomical and functional immaturity. Even with regular RI values, hypoxia causes arteriovenous shunting with blood supply to juxtamedullary nephrons and damage to the cortex, so the renal artery resistance index does not always represent the magnitude of renal tissue damage. Conclusions. Based on the findings, it can be concluded that SGA newborns are a high-risk category for developing AKI, which must be considered when treating this population of children. The use of more sensitive markers to avoid extreme AKI is needed since assessing renal functions solely on the basis of creatinine does not allow for an objective assessment of the degree of damage to the tubular apparatus. Key words: SGA infant, AGA infant, AKI (Acute Kidney Injury), Ischemic Nephropathy, KIM-1, NGAL, Cystatin C.
... Таким образом, у маловесных новорождён-ных с ИН различных степеней тяжести кон-центрации NGAL и KIM-1 повышаются на 1-е сутки жизни (p=0,001) что свидетельствует о повреждении эпителия канальцев почек уже в первые часы после ишемии, так как ни NGAL, ни KIM-1 не экспрессируются в мочу при нор-мальных почках, а высокие их концентрации в динамике (p=0,001) на 7-10-е сутки указыва-ют на степень тяжести и продолжительность ишемического повреждения почек. Наши ис-следования совпадают с недавними исследо-ваниями, проведёнными Hongzhu Lu и соавт., которые проверяли уровни этих биомаркё-ров в моче у недоношенных новорождённых с острым повреждением почек и также наблю-дали резкий и ранний подъём уровня KIM-1 и NGAL в моче при нормальной концентрации креатинина в плазме крови [9]. ...
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Aim. The study of the diagnostic value of KIM-1 and NGAL in urine and cystatin C in the blood plasma of low birth weight infants with ischemic nephropathy. Methods. 150 newborns were divided into 3 groups: main group 72 low birth weight infants with manifestations of ischemic nephropathy divided into three subgroups: group 1A mild (n=36), 1B moderate (n=20), 1C severe (n=16); comparioson group 28 low birth weight infants without the evidence of ischemic nephropathy; control group 50 healthy newborns (20 full-term and 30 preterm).To assess the state of tubular epithelium of the kidneys, the levels of KIM-1 and NGAL were measured in the urine of neonates, to assess the state of glomerular filtration the level of сystatin C in the blood plasma was determined. Samples of blood and urine were collected twice, on days 1 to 3 and 7 to 10. Biomarker levels were determined by solid-phase enzyme immunoassay. Results. In the main group on day 1 to 3 of life KIM-1 and NGAL in the urine were significantly elevated compared to the control group (p 0.001). On day 7 to 10 the level of KIM-1 in the urine in subgroup 1A decreased (0.980.09 ng/dl), while remaining significantly higher compared to the control group, and in subgroups 1B and 1C it increased to 1.240.10 and 1.360.12 ng/dl, respectively. On day 7 to 10 of life the concentration of NGAL in the urine of children of all three subgroups declined, remaining significantly high compared to the control values. Сoncentration of cystatin C was significantly high only in newborns of subgroup 1C (p 0.001). Conclusion. Molecules of NGAL and KIM-1 are early markers of the renal ischemic injury in low birth weight infants who suffered perinatal hypoxia, and cystatin C cannot be considered an early predictor of renal damage in low birth weight infants with ischemic nephropathy as its level in the blood rises only in severe damage.
Drug-induced nephrotoxicity is widespread and seriously affects human health. Vancomycin is a classical glycopeptide antibiotic. Vancomycin is widely used for severe infections caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus but its obvious nephrotoxicity affects the safety of its clinical application. However, the etiology of vancomycin induced kidney injury is not well understood. This study aimed to explore the potential mechanism of vancomycin-induced nephrotoxicity in rats. Vancomycin (400 mgkg ⁻¹ ) was used to establish kidney injury models in rats. A metabonomic approach was employed using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to delineate metabolic alterations. As a result, 15, 22, and 37 biomarkers were identified in urine samples from the treatment group compared to the control model on D2, D4, and D7, respectively. Changes in the levels of these metabolites indicated that amino acid metabolism and energy metabolism were disturbed in rats with vancomycin-associated nephrotoxicity. This study revealed the kidney effect of vancomycin, which may provide novel and promising research approaches to vancomycin-induced renal toxicity.
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Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although used in clinical practice, serum creatinine (SCr) is insensitive for early diagnosing AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers of which the performance in pediatric ICU patients is largely unknown. We aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties to identify children at risk for AKI development. From June 2010 until January 2014 we conducted a prospective observational cohort study of term-born children aged one day to one year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12 hours up to 72 hours post-admission. Blood samples were assayed for SCr; urine samples for uNGAL and KIM-1. The RIFLE classification (Risk, Injury, or Failure as 150%, 200% or 300% of median SCr reference values) was used to define AKI. 100 children were included (80 survived). Median age at admission was 27.7 days (IQR 1.5-85.5); median duration of mechanical ventilation was 5.8 days (IQR 3.1-11.4). Thirty-five patients had evidence of AKI within the first 48 hours post-admission of whom 24 (69%) already had AKI when entering the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12 hours and 12 to 24 hours post-admission, respectively. The maximal ROC-AUC for uNGAL was 0.815 (95%CI 0.685-0.945, P-value < 0.001) at 0 to 6 hours post-admission. The discriminative ability of KIM-1 was moderate with a largest AUC of 0.737 (95%CI 0.628-0.847, P-value < 0.001) at 12 to 24 hours post-admission. At the optimal cut-off point (126 ng/mL), uNGAL concentration predicted AKI development correctly in 16 out of 19 (84%) children, up to 24 hours before a rise in SCr became apparent. Levels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12 hours and 12 to 24 hours, respectively. uNGAL seems a reliable marker for identifying children who will develop AKI 24 hours later.
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Background We prospectively assessed the feasibility of two urinary markers of renal injury as potential diagnostic tests for acute febrile urinary tract infection (UTI) and subsequent renal scarring. Methods The patient cohort comprised children aged 0 to 4 years who visited the emergency room. The children were divided into three groups, namely, a febrile UTI (fUTI), febrile control (FC) and a non-febrile control (NFC) group, respectively, which were matched for sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on urine collected from each child. The urine levels of both markers were compared between the three groups, and the diagnostic accuracy was determined based on the area under the receiver-operator characteristic curve (AUC). In the fUTI group, the predictability of subsequent renal scarring was assessed by associating urinary levels with dimercaptosuccinic acid findings 6 months after an UTI episode. Results Significantly elevated levels of urinary NGAL and KIM-1 were observed in the fUTI group, as well as with increased urine esterase, serum C-reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The AUC of KIM-1 for the prediction of scarring was 71 % (p
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Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.
Discovery and qualification of novel biomarkers with improved specificity and sensitivity for detection of xenobiotic-induced injuries is an area of active research across multiple sectors. However, the majority of efforts in this arena have used genetically limited rodent stocks that lack variability in xenobiotic responses inherent to genetically heterogeneous human populations. In this study, genetically diverse Diversity Outbred (DO) mice were used as a surrogate for human clinical populations to investigate performance of urinary kidney biomarkers against classical preclinical kidney injury biomarkers (blood urea nitrogen [BUN] and serum creatinine). In this study, cisplatin was used as a paradigm kidney toxicant, with female adult DO mice exposed to a single injection (5 mg/kg) of cisplatin or vehicle and necropsied 72 h post-exposure and 18 h following overnight urine collection. Interindividual variability in kidney toxicity was observed, with DO mice experiencing either no tubule cell necrosis or minimal-mild necrosis. A panel of urinary protein biomarkers and profiled miRNAs were assessed by receiver-operating characteristic curves as to their ability to distinguish non-responder versus responder animals, as defined by histopathological evidence of renal tubule cell necrosis. A surprising outcome of these studies was that BUN was elevated alongside of urinary miRNA and protein biomarkers in animals with grade 2 proximal tubular cell necrosis; but not elevated with grade 1 necrosis. These studies demonstrate a novel approach for using a rodent population to better assess sensitivity of candidate biomarkers, especially for proposed clinical applications. Impact statement Recent studies have indicated that several urinary proteins and miRNA species may be suitable as biomarkers for acute kidney injury. A major focus on biomarker qualification is demonstrating improved specificity and sensitivity over gold standard tests. In this study, a mouse population model, Diversity Outbred mice, was used to demonstrate that neither the urinary protein markers nor the miRNA species assayed in urine could reliably detect low severity kidney injury better than blood urea nitrogen. This study has implications for use of these biomarkers in the clinic, where interindividual heterogeneity is present within patient populations and for which the underlying tissue pathology may not be known.
Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies. Emerging biomarkers which require further study in the neonatal population include netrin-1 and EGF. Increased awareness amongst clinicians of nephrotoxic medications being a modifiable risk factor for the development of neonatal acute kidney injury is imperative. The burden of chronic kidney failure following neonatal acute kidney injury is unclear and requires further study.
Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p < 0.001, p <0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p = 0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p = 0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.
Background: Acute Kidney Injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. Methods: We performed a case control study on a prospective cohort of preterm infants (<32 weeks), to compare 7 urine biomarkers between 25 infants with AKI and 20 infants without AKI. Results: Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 µg/ml vs. 4.24 µg/ml; p<0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 µg/ml vs. 0.006 µg/ml; p<0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). Conclusion: Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.Pediatric Research (2016); doi:10.1038/pr.2016.70.
Progress in treating human acute renal failure (ARF) is dependent on developing techniques that allow for the rapid diagnosis, quantification of injury, further understanding of the pathophysiology, and the effects of therapy. Therefore, four techniques that will facilitate this progress are described and illustrated by four different investigative teams. Techniques to measure rapid changes in GFR are available for rapid diagnosis and quantification of ARF in humans. State-of-the-art magnetic resonance imaging (MRI) presently allows for enhanced resolution of regional renal blood flow and functional evaluations in patients. Furthermore, new probes and techniques for MRI that allow for identification and quantitation of inflammation, applicable to human ARF, are being developed and tested in animal models. Finally, two-photon microscopy will allow for four-dimensional cellular and subcellular studies in animal models of ARF providing rapid insights into pathophysiology and the therapeutic effects of a variety of promising agents. Further development and utilization of these techniques, especially in concert with genetic, proteomic, and molecular approaches, will allow for needed insights into the pathophysiology and therapy in human ARF. E-mail:
The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.