Аннотация
Нейтрофильный желатиназа-ассоциированный липокалин (Neutrophil Gelatinaze Associated
Lipocalin, NGAL) представляет собой один из маркеров острого почечного повреждения, проблема развития и лечения которого является актуальной. В детской кардиохирургии ее актуальность еще больше по причине сложности, объема оперативного вмешательства и анатомо-физиологических особенностей детей с врожденными пороками сердца. В статье представлена информация о биологической роли NGAL, дано отдельное описание u-NGAL и s-NGAL, их функций и механизма действия в норме и при патологии, в частности при развитии острого почечного повреждения. Описаны исследования по их применению в кардиохирургической практике
у детей. Приведено сравнение эффективности NGAL и сывороточного креатинина в диагностике острого почечного повреждения. Описаны исследования, показывающие преимущества
NGAL перед креатинином, являющимся традиционным маркером почечной недостаточности.
Отмечены особенности показателей креатинина, характерные для детского возраста и, в частности, для неонатального периода.
Литература
- Ricci Z., Villa G., Ronco C. Management of AKI: the
role of biomarkers. In: Vincent J.L. Annual Update in
Intensive Care and Emergency Medicine. Cham-
Heidelberg–New York–Dordzechr–London: Springer;
2015: 365–78. DOI: 10.1007/978-3-319-13761-2
- Ronco C., Kellum J.A., Haase M. Subclinical AKI is still
AKI. Crit. Care. 2012; 16 (3): 313. DOI: 10.1186/cc11240
- Greenberg J.H., Zappitelli M., Jia Y., Thiessen-
Philbrook H.R., de Fontnouvelle C.A., Wilson F.
Biomarkers of AKI progression after pediatric cardiac
surgery. J. Am. Soc. Nephrol. 2018; 29 (5): 1549–56. DOI: 10.1681/ASN.2017090989
- Nickolas T.L., Schmidt-Ott K.M., Canetta P.,
Forster C., Singer E., Sise M. et al. Diagnostic and
prognostic stratification in the emergency department
using urinary biomarkers of nephron damage:
a multicenter prospective cohort study. J. Am. Coll.
Cardiol. 2012; 59 (3): 246–55. DOI: 10.1016/j.jacc.2011.10.854
- Muthialu N. Risk factors and outcome of acute kidney
injury after congenital heart surgery. Ind. J. Crit. Care
Med. 2018; 22 (3): 198. DOI: 10.4103/ijccm.ijccm_508_17
- MacDonald C., on behalf of the Western Canadian Complex
Pediatric Therapies Follow-Up Group, Norris C.,
Alton G.Y., Urschel S., Joffe A.R., Morgan C.J. et al.
Acute kidney injury after heart transplant in young children:
risk factors and outcomes. Pediatr. Nephrol. 2016;
31 (4): 671–8. DOI: 10.1007/s00467-015-3252-x
- Борщикова Т.И., Кардаш С.В., Сергеева О.Н., Цыганова М.П. Применение почечно-заместительной терапии у детей Кемеровской области. Комплексные
проблемы сердечно-сосудистых заболеваний. 2016; 1:
77–85. DOI: 10.17802/2306-1278-2016-1-77-85
[Borshchikova T.I., Kardash S.V., Sergeeva O.N.,
Tsyganova M.P. The use of renal replacement therapy
in children in the Kemerovo Region. Kompleksnye
Problemy Serdechno-Sosudistyh Zabolevanij (Russian
Journal of Complex Issuses of Cardiovascular Diseases).
2016; 1: 77–85. (in Russ.). DOI: 10.17802/2306-1278-2016-1-77-85]
- Kaddourah A., Basu R.K., Bagshaw S.M., Goldstein S.L.,
Investigators A. Epidemiology of acute kidney injury in
critically ill children and young adults. N. Engl. J. Med.
2017; 5; 376 (1): 11–20. DOI: 10.1056/NEJMoa161139
- Koyner J.L., Garg A.X., Shlipak M.G., Patel U.D.,
Sint K., Hong K. et al. Urinary cystatin C and acute kidney
injury after cardiac surgery. Am. J. Kidney Dis. 2013;
61 (5): 730–8. DOI: 10.1053/j.ajkd.2012.12.006
- Svensson A.S., Kvitting J-P.E., Kovesdy C.P., Cederholm
I., Szabó Z. Changes in serum cystatin C, creatinine,
and C-reactive protein after cardiopulmonary
bypass in patients with normal preoperative kidney function.
Nephrology. 2016; 21 (6): 519–25. DOI: 10.1111/nep.12630
- Miró J., Rocío de la Vega, Gertz K.V., Jensen M.P.,
Engel J.M. Epidemiology of acute kidney injury in critically
ill children and young adults. N. Engl. J. Med. 2017;
376 (1): 11–20. DOI: 10.1056/nejmc1701196
- Tobias C.H., Philip H. Biomarkers for drug induced renal
damage and nephrotoxicity. AAPS J. 2011; 13: 615–31.
DOI: 10.1208/s12248-011-9301-x
- Huen S.C., Parikh C.R. Molecular phenotyping of clinical
AKI with novel urinary biomarkers. Am. J. Physiol.
Renal Physiol. 2015; 309: 406–13. DOI: 10.1152/ajprenal.00682.2014
- Schwartz G.J., Brion L.P., Spitzer A. The use of plasma
creatinine concentration for estimating glomerular filtration
rate in infants, children, and adolescents. Pediatr.
Clin. North. Am. 1987; 34: 571–90. DOI: 10.1016/s0031-3955(16)36251-4
- Staples A., LeBlond R., Watkins S., Wong C., Brandt J.
Validation of the revised Schwartz estimating equation in
a predominantly non-CKD population. Pediatr. Nephrol.
2010; 25: 2321–6. DOI: 10.1007/s00467-010-1598-7
- Brochner-Mortensen J., Rohbrandt K., Lauritzen R.B.
Precision of single injection. 51Cr. EDTA plasma clearance
and endogenous creatinine clearance determinations
in children. Scand. J. Clin. Lab. Invest. 1977; 37 (7):
625–9. DOI: 10.3109/00365517709100655
- Kuppens M., George I., Lewi L., Levtchenko E.,
Allegaert K. Creatinaemia at birth is equal to maternal
creatinaemia at delivery: docs this paradigm still hold?
J. Matern. Fetal. Neonatal. Med. 2012; 25: 978–80. DOI: 10.3109/14767058.2011.602144
- Pottel H., Vrydags N., Mahieu B., Vandewynckele E.,
Croes K., Martens F. Establishing age/sex related serum
creatinine reference intervals from hospital laboratory
data based on different statistical methods. Clin. Chim.
Acta. 2008; 396 (1–2): 49–55. DOI: 10.1016/j.cca.2008.06.017
- Seikaly M.G., Browne R., Bajaj G., Arant B.S. Jr.
Limitations to body length/serum creatinine ratio as an
estimate of glomerular filtration in children. Pediatr.
Nephrol. 1996; 10 (6): 709–11. DOI: 10.1007/s004670050195
- Ali R.M., Al-Shorbagy M.Y., Helmy M.W., El-Abhar H.S.
Role of Wnt4/β-catenin, Ang II/TGFβ, ACE2, NF-κB,
and IL-18 in attenuating renal ischemia/reperfusioninduced
injury in rats treated with Vit D and pioglitazone.
Eur. J. Pharmacol. 2018; 831: 68–76. DOI: 10.1016/j.ejphar.2018.04.032
- Gómez-Puerta J.A., Ortiz-Reyes B., Urrego T., Vanegas-
García A.L. Mun~oz C.H., González L.A. et al. Urinary
neutrophil gelatinase-associated lipocalin and monocyte
chemoattractant protein 1 as biomarkers for lupus
nephritis in Colombian SLE patient. Lupus. 2017; 27 (4):
637–46. DOI: 10.1177/0961203317738226
- Washino I., Hosohata K., Jin D., Takai S., Miyagawa T.
Early urinary biomarkers of renal tubular damage by
a high-salt intake independent of blood pressure in normotensive
rats. Clin. Exp. Pharmacol. Physiol. 2018;
45 (3): 261–8. DOI: 10.1111/1440-1681.12871
- Kwiatkowski D.M., Sutherland S.M. Acute kidney injury
in pediatric patients. Best Practice Res. Clin. Anaesth.
2017; 6: 380–7. DOI: 10.1053/j.ackd.2017.09.007
- Cheng Z., Panfilo O., Jeffrey F., Kevin R., Ryan W.,
Frank G. et al. Structural characterization of glycoprotein
NGAL, an early predictive biomarker for acute kidney
injury. Carbohydr. Res. 2010; 345: 2252–61. DOI: 10.1016/j.carres.2010.07.024
- Satirapoj B. Tubulointerstitial biomarkers for diabetic
nephropathy. J. Diabetes Res. 2018; 2018: 2852398. DOI: 10.1155/2018/2852398
- Jotwani V., Katz R., Ix J.H., Gutiérrez O.M., Bennett M.,
Parikh C.R. et al. Urinary biomarkers of kidney tubular
damage and risk of cardiovascular disease and mortality
in elders. Am. J. Kidney Dis. 2018; 18: 301–4. DOI: 10.1053/j.ajkd.2017.12.013
- Lisowska-Myjak B., Skarńyżska E., Wilczyńska P.,
Jakimiuk A. Correlation between the concentrations of
lactoferrin and neutrophil gelatinase-associated lipocalin
in meconium. Biometals. 2018; 31 (1): 123–9. DOI: 10.1007/s10534-017-0073-3
- Gupta S., Jackson A.R., DaJusta D.G., McLeod D.J.,
Alpert S.A., Jayanthi V.R. et al. Urinary antimicrobial
peptides: Potential novel biomarkers of obstructive
uropathy. J. Pediatr. Urol. 2018; 18: 2–18. DOI: 10.1016/j.jpurol.2018.03.006
- Rybi-Szumińska A., Wasilewska A., Litwin M., Kułaga Z.,
Szumiński M. Paediatric normative data for urine
NGAL/creatinine ratio. Acta Paediatr. 2013; 102 (6):
269–72. DOI: 10.1111/apa.12200
- Haase-Fielitz A.L., Haase M., Devarajan P. Neutrophil
gelatinase-associated lipocalin as a biomarker of acute
kidney injury: a critical evaluation of current status. Ann.
Clin. Biochem. 2014; 51 (3): 335–51. DOI: 10.1177/0004563214521795
- Singer S.E., Markó L., Paragas N., Barasch J., Dragun
D., Müller D.N. et al. Neutrophil gelatinase-associated
lipocalin: pathophysiology and clinical applications.
Acta Physiol. (Oxf). 2013; 207 (4): 663–72. DOI: 10.1111/apha.12054
- Kari J.A., Shalaby M.A., Sofyani K., Sanad A.S.,
Ossra A.F., Halabi R.S. et al. Urinary neutrophil
gelatinase-associated lipocalin (NGAL) and serum
cystatin C measurements for early diagnosis of acute
kidney injury in children admitted to PICU. World
J. Pediatr. 2018; 14 (2): 134–42. DOI: 10.1007/s12519-017-0110-x
- Ma Q., Devarajan P. Induction of proapoptotic Daxx following
ischemic acute kidney injury. Kidney Int. 2008; 74:
310–8. DOI: 10.1038/ki.2008.192
- Arany I. When less is more: apoptosis during acute kidney
injury. Kidney Int. 2008; 74: 261–2. DOI: 10.1038/ki.2008.221
- Kališnik J.M., Hrovat E., Hrastovec A., Žibert J., Jerin A.,
Skitek M. et al. Creatinine, neutrophil gelatinase-associated
lipocalin, and cystatin C in determining acute kidney
injury after heart operations using cardiopulmonary
bypass. Artif. Organs. 2017; 41 (5): 481–9. DOI: 10.1111/aor.12779
- Coca S.G., Garg A.X., Thiessen-Philbrook H., Koyner
J.L., Patel U.D., Krumholz H.M. et al. Urinary biomarkers
of AKI and mortality 3 years after cardiac surgery.
J. Am. Soc. Nephrol. 2014; 25: 1063–71. DOI: 10.1681/asn.2013070742
- Hošková L., Franekova J., Málek I., Kautzner J.,
Szárszoi O., Jabor A. et al. Comparison of cystatin C and
NGAL in early diagnosis of acute kidney injury аfter
heart transplantation. Ann. of Transpl. 2016; 21: 329–45.
DOI: 10.12659/aot.896700
- Puthucheary Z.A., Rawal J., McPhail M. et al. Acute
skeletal muscle wasting in critical illness. JAMA. 2013;
310: 1591–600. DOI: 10.1001/jama.2013.278481
- Liu K.D., Thompson B.T., Ancukiewicz M., Steingrub
J.S., Douglas I.S., Matthay M.A. et al. Acute
kidney injury in patients with acute lung injury: impact
of fluid accumulation on classification of acute
kidney injury and associated outcomes. Crit. Care
Med. 2011; 39: 2665–71. DOI: 10.1097/ccm.0b013e318228234b
- Toda Y., Sugimoto K. AKI after pediatric cardiac surgery
for congenital heart diseases – recent developments in
diagnostic criteria and early diagnosis by biomarkers.
J. Intens. Care. 2017; 5 (1): 49. DOI: 10.1186/s40560-017-0242-z
- Nickolas T.L., Schmidt-Ott K.M., Canetta P., Forster
C., Singer E., Sise M. et al. Diagnostic and prognostic
stratification in the emergency department using urinary
biomarkers of nephron damage: a multicenter
prospective cohort study. J. Am. Coll. Cardiol. 2012; 59:
246–55. DOI: 10.1016/j.jacc.2011.10.854
- Antonucci E., Lippi G., Ticinesi A., Pigna F., Guida L.,
Morelli I. et al. Neutrophil gelatinase-associated
lipocalin (NGAL): a promising biomarker for the
early diagnosis of acute kidney injury (AKI). Acta
Biomed. 2014; 85 (3): 289–94. DOI: 10.2217/bmm.10.12
- Haase M., Kellum J.A., Ronco C. Subclinical AKI – an
emerging syndrome with important consequences. Nat.
Rev. Nephrol. 2012; 8 (12): 735–9. DOI: 10.1038/nrneph.2012.197
- Shyam R., Patel M.L., Sachan R., Kumar S.,
Pushkar D.K. Role of urinary neutrophil gelatinaseassociated
lipocalin as a biomarker of acute kidney injury
in patients with circulatory shock. Ind. J. Crit. Care
Med. 2017; 21 (11): 740–5. DOI: 10.4103/ijccm.IJCCM_315_17
- Bennett M., Dent C.L., Ma Q., Dastrala S., Grenier F.,
Workman R. et al. Urine NGAL predicts severity of acute
kidney injury after cardiac surgery: a prospective study.
Clin. J. Am. Soc. Nephrol. 2008; 3: 665–73.
- Krawczeski C.D., Woo J.G., Wang Y., Bennett M.R.,
Ma Q., Devarajan P. Neutrophil gelatinase-associated
lipocalin concentrations predict development of acute
kidney injury in neonates and children after cardiopulmonary
bypass. J. Pediatr. 2011; 158: 1009–15. DOI: 10.1016/j.jpeds.2010.12.057
- McIlroy D.R., Wagener G., Lee H.T. Neutrophil gelatinase-
associated lipocalin and acute kidney injury after
cardiac surgery: the effect of baseline renal function on
diagnostic performance. Clin. J. Am. Soc. Nephrol. 2010;
5 (2): 211–9. DOI: 10.2215/CJN.04240609
- Еременко А.А., Минболатова Н.М. Острое повреждение почек у больных с синдромом полиорганной
недостаточности в раннем периоде после кардиохирургических операций. Анестезиология и реаниматология. 2015; 5: 38–41.
[Eremenko A.A., Minbolatova N.M. Acute kidney
damage in patients with the syndrome of multiple organ
failure in the early period after cardiac surgery.
Anesteziologiya i Reanimatologiya (Anesthesiology and
Resuscitation). 2015; 5: 38–41 (in Russ.).]
- Табакьян Е.А., Партигулов С.А., Бурмистрова И.В.,
Водясов В.Д., Булдакова Н.А., Коткина Т.И.,
Титов В.Н. Биомаркеры ишемии и острого повреждения почек после операций на сердце с искусственным кровообращением. Медицинский альманах.
2013; 4 (28): 30–4.
[Tabakyan E.A., Partigulov S.A., Burmistrova I.V.,
Vodyasov V.D., Buldakova N.A., Kotkina T.I., Titov V.N.
Biomarkers of ischemia and acute kidney damage after
operations on the heart with artificial blood circulation.
Meditsinskiy Al’manakh (Medical Almanac). 2013; 4 (28):
30–4 (in Russ.).]
- Mahmoodpoor A., Hamishehkar H., Fattahi V., Sanaie
S., Arora P., Nader N.D. Urinary versus plasma
neutrophil gelatinase-associated lipocalin (NGAL) as
a predictor of mortality for acute kidney injury in intensive
care unit patients. J. Clin. Anesth. 2018; 44: 12–7.
DOI: 10.1016/j.jclinane.2017.10.010
- Nusca A., Miglionico M., Proscia C., Ragni L., Carassiti
M., Lassandro Pepe F., Di Sciascio G. et al. Early
prediction of contrast-induced acute kidney injury by
a “bedside” assessment of neutrophil gelatinase-associated
lipocalin during elective percutaneous coronary interventions.
PLoS One. 2018; 13 (5): 193–7. DOI: 10.1371/journal. pone.0197833
- Tkaczyk M., Tomczyk D., Jander A., Góreczny S.,
Moszura T., Dryżek P. et al. Glomerular filtration
decrease after diagnostic cardiac catheterisation in children
with congenital cardiac malformation – the role of
serum creatinine, cystatin C, neutrophil gelatinase and
urine output monitoring. Postępy Kardiololi i Interwencyjnej
(Adv. Interv. Cardiol.). 2018; 14 (1): 67–74. DOI: 10.5114/aic.2018.74357
- Ghonemy T.A., Amro G.M. Plasma neutrophil gelatinase-
associated lipocalin (NGAL) and plasma cystatin C
(CysC) as biomarker of acute kidney injury after cardiac
surgery. Saudi J. Kidney Dis. Transpl. 2014; 25 (3): 582–5.
DOI: 10.4103/1319-2442.132194
- Dent C.L., Ma Q., Dastrala S., Bennett M., Mitsnefes
M.M., Barasch J. et al. Plasma neutrophil gelatinaseassociated
lipocalin predicts acute kidney injury, morbidity
and mortality after pediatric cardiac surgery:
a prospective uncontrolled cohort study. Crit. Care. 2007;
11 (6): 127. DOI: 10.1186/cc6192
Об авторах
- Ивкин Артём Александрович, клинический ординатор КемГМУ, лаборант-исследователь лаборатории критических состояний НИИ КПССЗ; orcid.org/0000-0002-3899-1642
-
Корнелюк Роман Александрович, мл. науч. сотр. НИИ КПССЗ, ассистент кафедры КемГМУ;
-
Шукевич Дмитрий Леонидович, доктор мед. наук, профессор кафедры КемГМУ, заведующий лабораторией критических состояний НИИ КПССЗ
