Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.
Adolescent
Biomarkers
/ blood
Case-Control Studies
Child
Creatinine
/ urine
Fatty Acid-Binding Proteins
/ blood
Female
Follow-Up Studies
Glomerular Filtration Rate
/ physiology
Humans
Interleukin-18
/ blood
Kidney
/ physiopathology
Lipocalin-2
/ blood
Longitudinal Studies
Male
Prognosis
Prospective Studies
Reference Values
Renal Insufficiency, Chronic
/ diagnosis
Renal Replacement Therapy
/ statistics & numerical data
Risk Assessment
/ methods
Urethral Obstruction
/ blood
Biomarkers
CKiD
Children
Kidney
L-FABP
NGAL
Obstructive uropathy
Journal
Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
20
03
2020
accepted:
05
05
2020
revised:
01
05
2020
pubmed:
24
5
2020
medline:
3
7
2021
entrez:
24
5
2020
Statut:
ppublish
Résumé
Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.
Sections du résumé
BACKGROUND
Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification.
METHODS
Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine.
RESULTS
In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR).
CONCLUSIONS
In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.
Identifiants
pubmed: 32444926
doi: 10.1007/s00467-020-04602-7
pii: 10.1007/s00467-020-04602-7
pmc: PMC7502482
mid: NIHMS1598226
doi:
Substances chimiques
Biomarkers
0
FABP1 protein, human
0
Fatty Acid-Binding Proteins
0
IL18 protein, human
0
Interleukin-18
0
LCN2 protein, human
0
Lipocalin-2
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1907-1914Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK066143
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK066174
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK066116
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK082194
Pays : United States
Commentaires et corrections
Type : CommentIn
Références
Immunol Lett. 2005 Jun 15;99(1):30-5
pubmed: 15894108
Pediatr Nephrol. 2007 Jan;22(1):101-8
pubmed: 17072653
Int Immunopharmacol. 2011 Aug;11(8):992-6
pubmed: 21354353
Kidney Int. 2009 Sep;76(5):500-11
pubmed: 19536084
JAMA Pediatr. 2018 Feb 1;172(2):174-180
pubmed: 29255845
Pediatrics. 2019 Mar;143(3):
pubmed: 30709926
Pediatr Nephrol. 2015 Apr;30(4):677-85
pubmed: 25348707
Pediatr Transplant. 2003 Aug;7(4):321-35
pubmed: 12890012
Scand J Clin Lab Invest Suppl. 2008;241:89-94
pubmed: 18569973
Kidney Int Rep. 2018 Jun 20;3(5):1183-1192
pubmed: 30197985
Pediatr Nephrol. 2017 Dec;32(12):2319-2330
pubmed: 28762101
J Pediatr Urol. 2015 Oct;11(5):249.e1-6
pubmed: 26096437
Blood Purif. 2005;23(2):144-8
pubmed: 15677863
Am J Kidney Dis. 2009 Dec;54(6):1012-24
pubmed: 19850388
Nephrology (Carlton). 2011 Aug;16(6):539-44
pubmed: 21504508
Am J Pathol. 2004 Oct;165(4):1243-55
pubmed: 15466390
J Immunol. 1999 May 1;162(9):5506-10
pubmed: 10228031
Exp Ther Med. 2018 May;15(5):4426-4430
pubmed: 29731827
Arthritis Rheum. 2002 Nov;46(11):3083-95
pubmed: 12428253
Cytokine. 2011 May;54(2):218-21
pubmed: 21356600
Pediatr Nephrol. 2017 Mar;32(3):377-381
pubmed: 27785626
Clin J Am Soc Nephrol. 2006 Sep;1(5):1006-15
pubmed: 17699320
J Am Soc Nephrol. 2005 Oct;16(10):3046-52
pubmed: 16148039
Pediatr Nephrol. 2019 Mar;34(3):443-448
pubmed: 30317433
PLoS One. 2013;8(1):e54863
pubmed: 23349979
Int Heart J. 2018 Jul 31;59(4):786-790
pubmed: 30022770
Clin Pediatr (Phila). 2002 Jun;41(5):309-14
pubmed: 12086196
Semin Nephrol. 2007 Jan;27(1):98-114
pubmed: 17336692
Am J Kidney Dis. 2004 Mar;43(3):405-14
pubmed: 14981598
Indian J Nephrol. 2015 Sep-Oct;25(5):269-73
pubmed: 26628791
J Pediatr Urol. 2018 Jun;14(3):238.e1-238.e6
pubmed: 29706289
J Int Med Res. 2011;39(6):2201-8
pubmed: 22289535
J Biochem Mol Toxicol. 2017 Nov;31(11):
pubmed: 28759707
Dis Markers. 2018 Sep 13;2018:1015726
pubmed: 30327688
J Am Soc Nephrol. 2009 Mar;20(3):629-37
pubmed: 19158356