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Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

Objectives To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). Methods In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [... Full description

Journal Title: Pediatric nephrology (Berlin West), 2018-08-29, Vol.34 (1), p.117-128
Main Author: Brunner, Hermine I
Other Authors: Gulati, Gaurav , Klein-Gitelman, Marisa S , Rouster-Stevens, Kelly A , Tucker, Lori , Ardoin, Stacey P , Onel, Karen B , Mainville, Rylie , Turnier, Jessica , Aydin, Pinar Ozge Avar , Witte, David , Huang, Bin , Bennett, Michael R , Devarajan, Prasad
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0931-041X
Link: https://www.ncbi.nlm.nih.gov/pubmed/30159624
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title: Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus
format: Article
creator:
  • Brunner, Hermine I
  • Gulati, Gaurav
  • Klein-Gitelman, Marisa S
  • Rouster-Stevens, Kelly A
  • Tucker, Lori
  • Ardoin, Stacey P
  • Onel, Karen B
  • Mainville, Rylie
  • Turnier, Jessica
  • Aydin, Pinar Ozge Avar
  • Witte, David
  • Huang, Bin
  • Bennett, Michael R
  • Devarajan, Prasad
subjects:
  • Adiponectin
  • Adiponectin - urine
  • Adolescent
  • Area Under Curve
  • Article
  • Biological markers
  • Biomarker
  • Biomarkers
  • Biomarkers - urine
  • Biopsy
  • Ceruloplasmin
  • Child
  • Children
  • Chronicity
  • Complications and side effects
  • Creatinine
  • Damage
  • Diagnosis
  • Disease Progression
  • Fatty acid-binding protein
  • Fatty liver
  • Female
  • Gelatinase
  • Glomerular filtration rate
  • Health aspects
  • Humans
  • Kidney - pathology
  • Kidney - physiopathology
  • Kidney diseases
  • Kidney Failure, Chronic - diagnosis
  • Kidney Failure, Chronic - physiopathology
  • Kidney Failure, Chronic - urine
  • Kidney Function Tests - methods
  • Kidneys
  • Lipocalin
  • Liver
  • Longitudinal Studies
  • Lupus
  • Lupus nephritis
  • Lupus Nephritis - pathology
  • Lupus Nephritis - physiopathology
  • Lupus Nephritis - urine
  • Male
  • Medicine
  • Medicine & Public Health
  • Monocyte chemoattractant protein 1
  • Monocytes
  • Nephritis
  • Nephrology
  • Original Article
  • Osteopontin
  • Osteopontin - urine
  • Pediatrics
  • Prognosis
  • Prospective Studies
  • Proteins
  • Proteinuria
  • Renal function
  • Risk factors
  • Systemic lupus erythematosus
  • Transferrin
  • Urine
  • Urology
  • Validation
ispartof: Pediatric nephrology (Berlin, West), 2018-08-29, Vol.34 (1), p.117-128
description: Objectives To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). Methods In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy. Results Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient ( r ) = − 0.49; p   0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p  
language: eng
source:
identifier: ISSN: 0931-041X
fulltext: no_fulltext
issn:
  • 0931-041X
  • 1432-198X
url: Link


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titleUrine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus
creatorBrunner, Hermine I ; Gulati, Gaurav ; Klein-Gitelman, Marisa S ; Rouster-Stevens, Kelly A ; Tucker, Lori ; Ardoin, Stacey P ; Onel, Karen B ; Mainville, Rylie ; Turnier, Jessica ; Aydin, Pinar Ozge Avar ; Witte, David ; Huang, Bin ; Bennett, Michael R ; Devarajan, Prasad
creatorcontribBrunner, Hermine I ; Gulati, Gaurav ; Klein-Gitelman, Marisa S ; Rouster-Stevens, Kelly A ; Tucker, Lori ; Ardoin, Stacey P ; Onel, Karen B ; Mainville, Rylie ; Turnier, Jessica ; Aydin, Pinar Ozge Avar ; Witte, David ; Huang, Bin ; Bennett, Michael R ; Devarajan, Prasad
descriptionObjectives To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). Methods In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy. Results Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient ( r ) = − 0.49; p  < 0.0001] but not proteinuria ( r  = 0.20; p  > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p  < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p  = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP. Conclusion In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline. Key messages • Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.
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1EISSN: 1432-198X
2DOI: 10.1007/s00467-018-4049-5
3PMID: 30159624
languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAdiponectin ; Adiponectin - urine ; Adolescent ; Area Under Curve ; Article ; Biological markers ; Biomarker ; Biomarkers ; Biomarkers - urine ; Biopsy ; Ceruloplasmin ; Child ; Children ; Chronicity ; Complications and side effects ; Creatinine ; Damage ; Diagnosis ; Disease Progression ; Fatty acid-binding protein ; Fatty liver ; Female ; Gelatinase ; Glomerular filtration rate ; Health aspects ; Humans ; Kidney - pathology ; Kidney - physiopathology ; Kidney diseases ; Kidney Failure, Chronic - diagnosis ; Kidney Failure, Chronic - physiopathology ; Kidney Failure, Chronic - urine ; Kidney Function Tests - methods ; Kidneys ; Lipocalin ; Liver ; Longitudinal Studies ; Lupus ; Lupus nephritis ; Lupus Nephritis - pathology ; Lupus Nephritis - physiopathology ; Lupus Nephritis - urine ; Male ; Medicine ; Medicine & Public Health ; Monocyte chemoattractant protein 1 ; Monocytes ; Nephritis ; Nephrology ; Original Article ; Osteopontin ; Osteopontin - urine ; Pediatrics ; Prognosis ; Prospective Studies ; Proteins ; Proteinuria ; Renal function ; Risk factors ; Systemic lupus erythematosus ; Transferrin ; Urine ; Urology ; Validation
ispartofPediatric nephrology (Berlin, West), 2018-08-29, Vol.34 (1), p.117-128
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1Gulati, Gaurav
2Klein-Gitelman, Marisa S
3Rouster-Stevens, Kelly A
4Tucker, Lori
5Ardoin, Stacey P
6Onel, Karen B
7Mainville, Rylie
8Turnier, Jessica
9Aydin, Pinar Ozge Avar
10Witte, David
11Huang, Bin
12Bennett, Michael R
13Devarajan, Prasad
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0Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus
1Pediatric nephrology (Berlin, West)
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0Pediatr Nephrol
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descriptionObjectives To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). Methods In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy. Results Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient ( r ) = − 0.49; p  < 0.0001] but not proteinuria ( r  = 0.20; p  > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p  < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p  = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP. Conclusion In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline. Key messages • Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.
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14Complications and side effects
15Creatinine
16Damage
17Diagnosis
18Disease Progression
19Fatty acid-binding protein
20Fatty liver
21Female
22Gelatinase
23Glomerular filtration rate
24Health aspects
25Humans
26Kidney - pathology
27Kidney - physiopathology
28Kidney diseases
29Kidney Failure, Chronic - diagnosis
30Kidney Failure, Chronic - physiopathology
31Kidney Failure, Chronic - urine
32Kidney Function Tests - methods
33Kidneys
34Lipocalin
35Liver
36Longitudinal Studies
37Lupus
38Lupus nephritis
39Lupus Nephritis - pathology
40Lupus Nephritis - physiopathology
41Lupus Nephritis - urine
42Male
43Medicine
44Medicine & Public Health
45Monocyte chemoattractant protein 1
46Monocytes
47Nephritis
48Nephrology
49Original Article
50Osteopontin
51Osteopontin - urine
52Pediatrics
53Prognosis
54Prospective Studies
55Proteins
56Proteinuria
57Renal function
58Risk factors
59Systemic lupus erythematosus
60Transferrin
61Urine
62Urology
63Validation
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titleUrine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus
authorBrunner, Hermine I ; Gulati, Gaurav ; Klein-Gitelman, Marisa S ; Rouster-Stevens, Kelly A ; Tucker, Lori ; Ardoin, Stacey P ; Onel, Karen B ; Mainville, Rylie ; Turnier, Jessica ; Aydin, Pinar Ozge Avar ; Witte, David ; Huang, Bin ; Bennett, Michael R ; Devarajan, Prasad
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7Biomarkers
8Biomarkers - urine
9Biopsy
10Ceruloplasmin
11Child
12Children
13Chronicity
14Complications and side effects
15Creatinine
16Damage
17Diagnosis
18Disease Progression
19Fatty acid-binding protein
20Fatty liver
21Female
22Gelatinase
23Glomerular filtration rate
24Health aspects
25Humans
26Kidney - pathology
27Kidney - physiopathology
28Kidney diseases
29Kidney Failure, Chronic - diagnosis
30Kidney Failure, Chronic - physiopathology
31Kidney Failure, Chronic - urine
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34Lipocalin
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36Longitudinal Studies
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38Lupus nephritis
39Lupus Nephritis - pathology
40Lupus Nephritis - physiopathology
41Lupus Nephritis - urine
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43Medicine
44Medicine & Public Health
45Monocyte chemoattractant protein 1
46Monocytes
47Nephritis
48Nephrology
49Original Article
50Osteopontin
51Osteopontin - urine
52Pediatrics
53Prognosis
54Prospective Studies
55Proteins
56Proteinuria
57Renal function
58Risk factors
59Systemic lupus erythematosus
60Transferrin
61Urine
62Urology
63Validation
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7Mainville, Rylie
8Turnier, Jessica
9Aydin, Pinar Ozge Avar
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7Mainville, Rylie
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9Aydin, Pinar Ozge Avar
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abstractObjectives To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). Methods In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy. Results Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient ( r ) = − 0.49; p  < 0.0001] but not proteinuria ( r  = 0.20; p  > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p  < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p  = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP. Conclusion In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline. Key messages • Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.
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