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

Hermine I. Brunner*, Gaurav Gulati, Marisa S Klein-Gitelman, Kelly A. Rouster-Stevens, Lori Tucker, Stacey P. Ardoin, Karen B. Onel, Rylie Mainville, Jessica Turnier, Pinar Ozge Avar Aydin, David Witte, Bin Huang, Michael R. Bennett, Prasad Devarajan

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 < 0.0001] 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.

Original languageEnglish (US)
Pages (from-to)117-128
Number of pages12
JournalPediatric Nephrology
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2019

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Lupus Nephritis
Systemic Lupus Erythematosus
Biomarkers
Urine
Kidney
Osteopontin
Adiponectin
Glomerular Filtration Rate
Fatty Acid-Binding Proteins
Transforming Growth Factors
Transferrin
Biopsy
ROC Curve
Area Under Curve
Vitamin D-Binding Protein
Pediatrics
Ceruloplasmin
Chemokine CCL2
Creatinine
Regression Analysis

Keywords

  • Biomarker
  • Children
  • Chronicity
  • Damage
  • Lupus nephritis
  • Validation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

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. / Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus. In: Pediatric Nephrology. 2019 ; Vol. 34, No. 1. pp. 117-128.
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title = "Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus",
abstract = "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} (TGF{\ss}), 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 TGF{\ss}, 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.",
keywords = "Biomarker, Children, Chronicity, Damage, Lupus nephritis, Validation",
author = "Brunner, {Hermine I.} and Gaurav Gulati and Klein-Gitelman, {Marisa S} and Rouster-Stevens, {Kelly A.} and Lori Tucker and Ardoin, {Stacey P.} and Onel, {Karen B.} and Rylie Mainville and Jessica Turnier and Aydin, {Pinar Ozge Avar} and David Witte and Bin Huang and Bennett, {Michael R.} and Prasad Devarajan",
year = "2019",
month = "1",
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doi = "10.1007/s00467-018-4049-5",
language = "English (US)",
volume = "34",
pages = "117--128",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
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Brunner, HI, Gulati, G, Klein-Gitelman, MS, Rouster-Stevens, KA, Tucker, L, Ardoin, SP, Onel, KB, Mainville, R, Turnier, J, Aydin, POA, Witte, D, Huang, B, Bennett, MR & Devarajan, P 2019, 'Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus', Pediatric Nephrology, vol. 34, no. 1, pp. 117-128. https://doi.org/10.1007/s00467-018-4049-5

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

In: Pediatric Nephrology, Vol. 34, No. 1, 01.01.2019, p. 117-128.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

AU - Brunner, Hermine I.

AU - Gulati, Gaurav

AU - Klein-Gitelman, Marisa S

AU - Rouster-Stevens, Kelly A.

AU - Tucker, Lori

AU - Ardoin, Stacey P.

AU - Onel, Karen B.

AU - Mainville, Rylie

AU - Turnier, Jessica

AU - Aydin, Pinar Ozge Avar

AU - Witte, David

AU - Huang, Bin

AU - Bennett, Michael R.

AU - Devarajan, Prasad

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 < 0.0001] 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.

AB - 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 < 0.0001] 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.

KW - Biomarker

KW - Children

KW - Chronicity

KW - Damage

KW - Lupus nephritis

KW - Validation

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