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Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in

critically ill multiple trauma patients

Aspek Penilaian
Latar Belakang Epidemiologi Acute kidney injury (AKI) is a frequent complication of severe
trauma; in a retrospective cohort of 1033 critically ill adult
trauma patients, the prevalence of AKI was 23.8% (1). Although
only 10% of these patients were in need of renal replacement
therapy, the presence of even mild AKI was associated with an
almost 2-fold increase in intensive care unit (ICU) mortality, as
well as greater duration of mechanical ventilation and length of
stay (1). It should be noted that the definition of AKI used by
Brandt et al. corresponds to the serum creatinine cut-off point
for the presence of risk (R) stage of AKI according to the risk
injury failure loss and end-stage kidney classification (RIFLE)
criteria (2). A shortcoming of creatinine-based methods for
detection of AKI is that serum creatinine is often affected only
after 48 h or more have elapsed from the initial attack. Such
delays in the diagnosis of AKI have been held responsible for
the lack of effect observed up to now in attempts of renal
protection. The search for a reliable real-time marker of AKI is
thus clinically relevant, as this would facilitate trials for early
renal-protective interventions (3, 4). Neutrophil gelatinase-
associated lipocalin (NGAL), a 25-kDa member of the lipocalin
family, has recently been proposed as an early marker of AKI,
shortlyafter injury and before an increase in serum creatinine
(4). In experimental animal models of renal injury, massive
induction in NGAL mRNA and protein has been observed in the
renal tubules, reaching 1000-fold in the most severe cases (5–
8). Expression of NGAL seems to exert a renal-protective effect
in this context (5). In humans, urinary NGAL (uNGAL) also seems
to represent an early, sensitive, non-invasive biomarker for AKI,
at least in certain high-risk groups (9–11). A large recent study
confirms that uNGAL is anaccurate marker of subsequent AKI in
unselectedadultpatients presenting to the emergency
department of a large hospital and outperforms serum
creatinine as well as other proposed markers of AKI wN-acetyl-
b-d-glucosaminidase (NAG), a1-microglobulin, a1-acid
glycoproteinx (12). The role of uNGAL as a predictor of AKI in
severe trauma has not been studied. The aim of this study was
to test the diagnostic value of uNGAL in the prediction of early
AKI in multiple trauma patients who were admitted to the ICU
of a Trauma Center. We studied adult multiple trauma
patientsadmitted to the ICU of a Trauma Center. The study was
approved by the hospital Ethics Committee.Exclusion criteria
were: a) survival less than 5 days, b) severe head injury with a
Glasgow Coma Scale (GCS), of 3 and with loss of pupillary
reflexes during the first 5 days of injury, c) known cardiac or
chronic kidney disease, d) initial serum creatinine )1.5 mg/dL
(132.74 mmol/L), and e) more than 24 h elapsing from injury to
evaluation by the investigators. Upon admission and at 24 and
48 h, 5 mL of freeflowing urine was collected, centrifuged at
800=g for 5 min and then frozen to –208C. NGAL was measured
in these samples with an ELISA technique, using a commercially
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

available kitwNGAL Rapid ELISA KitCat. No. KIT 037 from


Antibodyshop (now Bioporto), Gentofte, Denmarkx. Serum
creatinine was measured daily with the Jaffe method on an
Aeroset biochemistry analyzer (Abbott Diagnostics, Chicago, IL,
USA). Variables recorded were demographics, injury severity
score (ISS), acute physiology and chronic health evaluation
version II (APACHE II) score, sequential organ failure assessment
(SOFA) score on the day of admission, presence or absence of
shock on day 1, and total number of packed red cells transfused
on day 1. The presence and severity of AKI as defined by the
RIFLE criteria (2) was assessed daily until day 5 on the basis of
diuresis and serum creatinine values. We investigated for
differences observed between patients with absence of AKI
(group A) and patients who developed AKI of at least risk (R)
severity at some time point during the observation period
(group B). The studied variables were a) demographics, b)
indices of trauma severity (ISS).
We studied 31 patients (25 male, 6 female), of whom 20 did not
develop AKI (group A), while 11 did (group B). On the basis of
RIFLE criteria, AKI was first diagnosed on day 1 in two patients,
on day 2 in eight patients and on day 3 in one patient.
Demographics, indices of severity, and laboratory data are
presented in Table 1. Figure 1 presents changes in uNGAL and
serum creatinine over time. There was a significant difference
in NGAL-0 between the two groups that persisted on the
subsequent 2 days (NGAL-1, NGAL-2). There was no significant
difference between NGAL-0, NGAL-1, and NGAL-2 within group
A or group B.
AKI was mild and transient in most cases: nine patients
developed AKI of risk (R) and two of injury (I) severity, while on
day 5 only four patients still had AKI w2 with stage (R) and 2
with stage (I)x. After the observation period, three patients
developed AKI of failure (F) severity, but this represented
deterioration of AKI established during the first 5 days in only
one patient. In all three cases, it was believed that sepsis and/or
exposure to nephrotoxic agents were responsible for the late
deterioration in renal function.
Tujuan Neutrophil gelatinase-associated lipocalin (NGAL), an iron-
transporting protein rapidly accumulating in the kidney tubules
and urine after nephrotoxic and ischemic insults, has been put
forward as an early, sensitive, non-invasive biomarker for acute
kidney injury (AKI). The aim of this study was to evaluate
urinary NGAL levels as a predictor of early AKI (first 5 days after
injury) in multi-trauma patients.
Metode We studied multi-trauma adult patients admitted to the
intensive care unit of a trauma hospital. Exclusion criteria were
a) known cardiac or chronic kidney disease, and b) initial
evaluation after more than 24 h had elapsed from injury.
Urinary NGAL was measured using an ELISA technique upon
admission and at 24 and 48 h. Presence of AKI was defined by
the risk injury failure loss and end-stage kidney classification
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

(RIFLE) criteria. Data are reported as median and interquartile


range.
Hasil A total of 31 patients (25 male, 6 female) were studied. NGAL
levels at admission were significantly higher among patients
who subsequently developed AKI w155.5 (50.5–205.9) ng/mL
vs. 8.0 (5.7–17.7) ng/mL, ps0.0000x and these higher levels
persisted over the following 2 days. On the basis of receiver-
operating characteristic analysis both NGAL and serum
creatinine baseline measurements could predict AKI warea
under the curve (95% confidence interval) 0.977 (0.823–0.980)
and 0.789 (0.556–0.906), respectivelyx, but the area under the
curve for NGAL was significantly larger (ps0.024). A cut-off point
)25 ng/mL for NGAL had a sensitivity of 0.91 and specificity of
0.95 in predicting AKI.
Simpulan Urinary NGAL can be used from the 1st day of injury as a
reliable predictor of early AKI in multi-trauma patients. Clin
Chem Lab Med 2009;47:79–82.
Referensi 1. Brandt MM, Falvo AJ, Rubinfeld IS, Blyden D, Durrani NK,
Horst HM. Renal dysfunction in trauma: even a little costs a lot.
J Trauma 2007;62:1362–4.
2. Bellomo R, Kellum JA, Ronco C. Defining andclassifying acute
renal failure: from advocacy to consensus and validation of the
RIFLE criteria. Intensive Care Med 2007; 33:409–13.
3. Westhuyzen J, Endre ZH, Reece G, Reith DM, Saltissi D,
Morgan TJ. Measurement of tubular enzymuria facilitates early
detection of acute renal impairment in the intensive care unit.
Nephrol Dial Transplant 2003;18: 543–51.
4. Endre ZH, Westhuyzen J. Early detection of acute kidney
injury: emerging new biomarkers. Nephrology 2008;13: 91–8.
5. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, et al.
Endocytic delivery of lipocalin-siderophore-iron complex
rescues the kidney from ischemia-reperfusion injury. J Clin
Invest 2005;115:610–21.
6. Supavekin S, Zhang W, Kucherlapati R, KaskelFJ,Moore LC,
Devarajan P. Differential gene expression following early renal
ischemia/reperfusion. Kidney Int 2003;63: 1714–24.
7. Devarajan PJ. Update on mechanisms of ischemic acute
kidney injury. J Am Soc Nephrol 2006;17:1503–20.
8. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al.
Identification of NGAL as a novel urinary biomarker for ischemic
injury. J Am Soc Nephrol 2003;14: 2534–43.
9. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C,
et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a
biomarker for acute renal injury after cardiac surgery. Lancet
2005;365:1231–8.
10. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN,
et al. Association between increases in urinary neutrophil
gelatinase-associated lipocalin and acute renal dysfunction after
adult cardiac surgery. Anesthesiology 2006;105:485–91.
11. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E,
Malyszko JS, Pawlak K, Mysliwiec M, et al. Could neutrophil
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

gelatinase-associated lipocalin and cystatin C predict the


development of contrast induced nephropathy after
percutaneous coronaryinterventionsinpatients
with stable angina and normal serum creatinine values? Kidney
Blood Press Res 2007;30:408–15.
12. Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA,
Barasch N, et al. Sensitivity and specificity of a single emergency
department measurement of urinary neutrophil gelatinase-
associated lipocalin for diagnosing acute kidney injury. Ann
Intern Med 2008;148:810–9.
13. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q,
Devarajan P, et al. Urine neutrophil gelatinase-associated
lipocalin is an early marker of acute kidney injury in critically ill
children: aprospectivecohortstudy.CritCare 2007;11:R84.
14. Xu SY, Pauksen K, Venge P. Serum measurements of human
neutrophil lipocalin (HNL) discriminate between acute bacterial
and viral infections. Scand J Clin Lab Invest 1995;55:125–31.
15. Carlson M, Raab Y, Seve´us L, Xu S, Ha¨llgren R, Venge P.
Human neutrophil lipocalin is a unique marker of neutrophil
inflammation in ulcerative colitis and proctitis. Gut
2002;50:501–6.
16. Hemdahl AL, Gabrielsen A, Zhu C, Eriksson P, Hedin U,
Kastrup J, et al. Expression of neutrophil gelatinaseassociated
lipocalin in atherosclerosis and myocardial infarction.
Arterioscler Thromb Vasc Biol 2006;26: 136–42.
17. Bu DX, Hemdahl AL, Gabrielsen A, Fuxe J, Zhu C, Eriksson P,
et al. Induction of neutrophil gelatinase-associated lipocalin in
vascular injury via activation of nuclear factor-kappaB. Am J
Pathol 2006;169:2245–53.
18. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M,
Cvijanovich N, et al. Serum neutrophil gelatinase-associated
lipocalin (NGAL) as a marker of acute kidney injury in critically ill
children with septic shock. Crit Care Med 2008;36:1297–303.
19. Suzuki M, Wiers KM, Klein-Gitelman MS, Haines KA, Olson J,
Onel KB, et al. Neutrophilgelatinase-associated lipocalin as a
biomarker of disease activity in pediatric lupus nephritis.
Pediatr Nephrol 2008;23:403–12.
20. Mori K, Nakao K. Neutrophil gelatinase-associated lipocalin
as the real-time indicator of active kidney damage. Kidney Int
2007;71:967–70.
21. Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J,
et al. Urinary neutrophil gelatinase-associated lipocalin in
DqHUS: a novel marker of renal injury. Pediatr Nephrol
2006;21:989–94.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

Aspek Penilaian
Latar Belakang Epidemiologi cedera ginjal akut (AKI) merupakan komplikasi yang sering
trauma yang parah; dalam kohort retrospektif dari 1033 pasien
trauma dewasa yang sakit kritis, prevalensi AKI adalah 23,8%
(1). Meskipun hanya 10% dari pasien ini membutuhkan terapi
pengganti ginjal, kehadiran bahkan ringan AKI dikaitkan dengan
peningkatan hampir 2 kali lipat di unit perawatan intensif (ICU)
mortalitas, serta durasi lebih besar dari ventilasi mekanis dan
panjang tinggal (1). Perlu dicatat bahwa definisi AKI digunakan
oleh Brandt et al. sesuai dengan kreatinin serum cut-off point
untuk kehadiran risiko (R) tahap AKI menurut cedera risiko
kegagalan kehilangan dan stadium akhir klasifikasi ginjal (RIFLE)
kriteria (2). Kelemahan dari metode berbasis kreatinin-untuk
mendeteksi AKI adalah bahwa kreatinin serum sering
terpengaruh setelah 48 jam atau lebih telah berlalu dari
serangan awal. penundaan tersebut dalam diagnosis AKI telah
bertanggung jawab atas kurangnya efek diamati sampai
sekarang dalam upaya perlindungan ginjal. Pencarian untuk
real-time marker diandalkan AKI demikian relevan secara klinis,
karena hal ini akan memfasilitasi uji coba untuk awal ginjal-
pelindung intervensi (3, 4). Neutrofil gelatinase terkait lipocalin
(NGAL), anggota 25-kDa dari keluarga lipocalin, baru-baru ini
diusulkan sebagai penanda awal AKI, shortlyafter cedera dan
sebelum peningkatan kreatinin serum (4). Dalam model hewan
percobaan cedera ginjal, induksi besar-besaran di NGAL mRNA
dan protein telah diamati di tubulus ginjal, mencapai 1000 kali
lipat dalam kasus yang paling parah (5-8). Ekspresi NGAL
tampaknya mengerahkan efek ginjal-protektif dalam konteks ini
(5). Pada manusia, NGAL kemih (uNGAL) juga tampaknya
mewakili awal, sensitif, biomarker non-invasif untuk AKI,
setidaknya di kelompok berisiko tinggi tertentu (11/9). Sebuah
studi baru-baru besar menegaskan bahwa uNGAL adalah
anaccurate penanda berikutnya AKI di unselectedadultpatients
menyajikan ke gawat darurat sebuah rumah sakit besar dan
melebihi kreatinin serum serta penanda diusulkan lain dari AKI
WN-asetil-bd-glucosaminidase (NAG), a1-mikroglobulin , a1-
asam glycoproteinx (12). Peran uNGAL sebagai prediktor AKI di
trauma berat belum diteliti. Tujuan dari penelitian ini adalah
untuk menguji nilai diagnostik uNGAL di prediksi awal AKI di
beberapa pasien trauma yang dirawat di ICU dari Trauma
Center. Kami mempelajari beberapa trauma dewasa
patientsadmitted ke ICU dari Trauma Center. Studi ini disetujui
oleh rumah sakit kriteria Etika Committee.Exclusion adalah: a)
kelangsungan hidup kurang dari 5 hari, b) cedera kepala berat
dengan Glasgow Coma Scale (GCS), dari 3 dan dengan hilangnya
refleks pupil selama 5 hari pertama cedera, c) jantung dikenal
atau penyakit ginjal kronis, d) awal serum kreatinin) 1,5 mg / dL
(132,74 mmol / L), dan e) lebih dari 24 jam elapsing dari cedera
untuk evaluasi oleh para peneliti. Setelah masuk dan pada 24
dan 48 jam, 5 mL freeflowing urine dikumpulkan, disentrifugasi
pada 800 = g selama 5 menit dan kemudian dibekukan untuk -
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

208C. NGAL diukur dalam sampel ini dengan teknik ELISA,


menggunakan tersedia secara komersial kitwNGAL cepat ELISA
KitCat. Tidak KIT 037 dari Antibodyshop (sekarang Bioporto),
Gentofte, Denmarkx. kreatinin serum diukur setiap hari dengan
metode Jaffe pada analisa biokimia Aeroset (Abbott
Diagnostics, Chicago, IL, USA). Variabel dicatat adalah
demografi, skor keparahan cedera (ISS), fisiologi akut dan versi
evaluasi kesehatan kronis II (APACHE II) skor, berurutan
penilaian kegagalan organ (SOFA) skor pada hari masuk, ada
atau tidak adanya kejutan pada hari 1, dan jumlah sel darah
merah dikemas ditransfusikan pada hari 1. keberadaan dan
tingkat keparahan AKI seperti yang didefinisikan oleh kriteria
RIFLE (2) dinilai setiap hari sampai hari 5 berdasarkan diuresis
dan serum nilai kreatinin. Kami menyelidiki perbedaan diamati
antara pasien dengan tidak adanya AKI (grup A) dan pasien yang
mengembangkan AKI minimal risiko (R) keparahan di beberapa
titik waktu selama periode pengamatan (kelompok B). Variabel
yang diteliti adalah a) demografi, b) indeks keparahan trauma
(ISS).
Kami mempelajari 31 pasien (25 laki-laki, 6 perempuan), di
antaranya 20 tidak berkembang AKI (grup A), sementara 11
melakukan (kelompok B). Atas dasar kriteria RIFLE, AKI pertama
kali didiagnosis pada hari 1 dalam dua pasien, pada hari 2 di
delapan pasien dan pada hari 3 dalam satu pasien. Demografi,
indeks keparahan, dan data laboratorium disajikan pada Tabel
1. Gambar 1 menyajikan perubahan uNGAL dan serum kreatinin
dari waktu ke waktu. Ada perbedaan yang signifikan dalam
NGAL-0 antara kedua kelompok yang berlangsung pada
berikutnya 2 hari (NGAL-1, NGAL-2). Tidak ada perbedaan yang
signifikan antara NGAL-0, NGAL-1, dan NGAL-2 dalam kelompok
A atau kelompok B.
AKI adalah ringan dan sementara dalam kebanyakan kasus:
sembilan pasien mengembangkan AKI risiko (R) dan dua cedera
(I) keparahan, sedangkan pada hari ke 5 hanya empat pasien
masih memiliki AKI w2 dengan tahap (R) dan 2 dengan stadium
(I) x. Setelah periode observasi, tiga pasien mengembangkan
AKI kegagalan (F) keparahan, tapi ini mewakili penurunan AKI
didirikan selama 5 hari pertama hanya satu pasien. Dalam
ketiga kasus, diyakini bahwa sepsis dan / atau paparan agen
nefrotoksik bertanggung jawab atas kerusakan di akhir fungsi
ginjal.
Tujuan Neutrofil gelatinase terkait lipocalin (NGAL), sebuah protein
besi-mengangkut cepat terakumulasi dalam tubulus ginjal dan
urin setelah penghinaan nefrotoksik dan iskemik, telah
dikemukakan sebagai awal, sensitif, biomarker non-invasif
untuk cedera ginjal akut (AKI). Tujuan dari penelitian ini adalah
untuk mengevaluasi tingkat NGAL urin sebagai prediktor awal
AKI (5 hari pertama setelah cedera) pada pasien multi-trauma.
Metode Kami mempelajari pasien dewasa multi-trauma dirawat di unit
perawatan intensif sebuah rumah sakit trauma. Kriteria eksklusi
adalah a) jantung dikenal atau penyakit ginjal kronis, dan b)
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

evaluasi awal setelah lebih dari 24 jam telah berlalu dari cedera.
Kemih NGAL diukur dengan menggunakan teknik ELISA pada
saat masuk dan pada 24 dan 48 jam. Kehadiran AKI
didefinisikan oleh cedera risiko kegagalan kehilangan dan
stadium akhir klasifikasi ginjal (RIFLE) kriteria. Data yang
dilaporkan sebagai median dan kisaran interkuartil.
Hasil Sebanyak 31 pasien (25 laki-laki, 6 perempuan) dipelajari.
tingkat NGAL saat masuk secara signifikan lebih tinggi di
antara pasien yang kemudian dikembangkan AKI w155.5
(50,5-205,9) ng / mL vs 8,0 (5,7-17,7) ng / mL, ps0.0000x
dan tingkat yang lebih tinggi bertahan selama 2 hari
berikut. Atas dasar analisis karakteristik receiver-operasi
baik NGAL dan pengukuran dasar kreatinin serum bisa
memprediksi AKI warea di bawah kurva (95% confidence
interval) 0,977 (0,823-0,980) dan 0,789 (0,556-0,906),
respectivelyx, tapi daerah di bawah kurva untuk NGAL
secara signifikan lebih besar (ps0.024). Sebuah cut-off
point) 25 ng / mL untuk NGAL memiliki sensitivitas 0,91
dan spesifisitas 0,95 dalam memprediksi AKI.

Simpulan NGAL kemih dapat digunakan dari 1 hari cedera sebagai


prediktor yang dapat diandalkan awal AKI pada pasien multi-
trauma. Clin Chem Lab Med 2009; 47: 79-82.
Referensi 1. Brandt MM, Falvo AJ, Rubinfeld IS, Blyden D, Durrani NK,
Horst HM. Renal dysfunction in trauma: even a little costs a lot.
J Trauma 2007;62:1362–4.
2. Bellomo R, Kellum JA, Ronco C. Defining andclassifying acute
renal failure: from advocacy to consensus and validation of the
RIFLE criteria. Intensive Care Med 2007; 33:409–13.
3. Westhuyzen J, Endre ZH, Reece G, Reith DM, Saltissi D,
Morgan TJ. Measurement of tubular enzymuria facilitates early
detection of acute renal impairment in the intensive care unit.
Nephrol Dial Transplant 2003;18: 543–51.
4. Endre ZH, Westhuyzen J. Early detection of acute kidney
injury: emerging new biomarkers. Nephrology 2008;13: 91–8.
5. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, et al.
Endocytic delivery of lipocalin-siderophore-iron complex
rescues the kidney from ischemia-reperfusion injury. J Clin
Invest 2005;115:610–21.
6. Supavekin S, Zhang W, Kucherlapati R, KaskelFJ,Moore LC,
Devarajan P. Differential gene expression following early renal
ischemia/reperfusion. Kidney Int 2003;63: 1714–24.
7. Devarajan PJ. Update on mechanisms of ischemic acute
kidney injury. J Am Soc Nephrol 2006;17:1503–20.
8. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al.
Identification of NGAL as a novel urinary biomarker for ischemic
injury. J Am Soc Nephrol 2003;14: 2534–43.
9. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C,
et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a
biomarker for acute renal injury after cardiac surgery. Lancet
2005;365:1231–8.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients

10. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN,


et al. Association between increases in urinary neutrophil
gelatinase-associated lipocalin and acute renal dysfunction after
adult cardiac surgery. Anesthesiology 2006;105:485–91.
11. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E,
Malyszko JS, Pawlak K, Mysliwiec M, et al. Could neutrophil
gelatinase-associated lipocalin and cystatin C predict the
development of contrast induced nephropathy after
percutaneous coronaryinterventionsinpatients
with stable angina and normal serum creatinine values? Kidney
Blood Press Res 2007;30:408–15.
12. Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA,
Barasch N, et al. Sensitivity and specificity of a single emergency
department measurement of urinary neutrophil gelatinase-
associated lipocalin for diagnosing acute kidney injury. Ann
Intern Med 2008;148:810–9.
13. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q,
Devarajan P, et al. Urine neutrophil gelatinase-associated
lipocalin is an early marker of acute kidney injury in critically ill
children: aprospectivecohortstudy.CritCare 2007;11:R84.
14. Xu SY, Pauksen K, Venge P. Serum measurements of human
neutrophil lipocalin (HNL) discriminate between acute bacterial
and viral infections. Scand J Clin Lab Invest 1995;55:125–31.
15. Carlson M, Raab Y, Seve´us L, Xu S, Ha¨llgren R, Venge P.
Human neutrophil lipocalin is a unique marker of neutrophil
inflammation in ulcerative colitis and proctitis. Gut
2002;50:501–6.
16. Hemdahl AL, Gabrielsen A, Zhu C, Eriksson P, Hedin U,
Kastrup J, et al. Expression of neutrophil gelatinaseassociated
lipocalin in atherosclerosis and myocardial infarction.
Arterioscler Thromb Vasc Biol 2006;26: 136–42.
17. Bu DX, Hemdahl AL, Gabrielsen A, Fuxe J, Zhu C, Eriksson P,
et al. Induction of neutrophil gelatinase-associated lipocalin in
vascular injury via activation of nuclear factor-kappaB. Am J
Pathol 2006;169:2245–53.
18. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M,
Cvijanovich N, et al. Serum neutrophil gelatinase-associated
lipocalin (NGAL) as a marker of acute kidney injury in critically ill
children with septic shock. Crit Care Med 2008;36:1297–303.
19. Suzuki M, Wiers KM, Klein-Gitelman MS, Haines KA, Olson J,
Onel KB, et al. Neutrophilgelatinase-associated lipocalin as a
biomarker of disease activity in pediatric lupus nephritis.
Pediatr Nephrol 2008;23:403–12.
20. Mori K, Nakao K. Neutrophil gelatinase-associated lipocalin
as the real-time indicator of active kidney damage. Kidney Int
2007;71:967–70.
21. Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J,
et al. Urinary neutrophil gelatinase-associated lipocalin in
DqHUS: a novel marker of renal injury. Pediatr Nephrol
2006;21:989–94.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in
critically ill multiple trauma patients