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
N1 - Funding Information:
Patients with childhood-onset systemic lupus erythematosus (cSLE) [30, 31] were required a kidney biopsy as part of standard of care participated in this longitudinal study. Clinical and laboratory information as well as random spot urine samples were collected at time of kidney biopsy and in regular intervals every 3 months (range 2–5 months) thereafter. The study complied with the Declaration of Helsinki and was approved by the institutional review boards of all of the participating institutions. This work was supported by the National Institutes of Health (U01AR059509 to HIB, P50DK096418 to PD and HIB, P30AR070549, and 5UL1TR001425).
Funding Information:
Funding acknowledgement This study is supported by grants from the NIH (U01 AR059509 to HB, P50 DK096418 to PD and HB, P30 AR070549-01 to Susan Thompson) and the Innovation Fund from CCHMC; the CCTST at the University of Cincinnati is funded by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, grant 5UL1TR001425-03. The CTSA program is led by the NIH’s National Center for Advancing Translational Sciences (NCATS). The content of this website is solely the responsibility of the CCTST and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2018, IPNA.
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
UR - http://www.scopus.com/inward/record.url?scp=85052676249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052676249&partnerID=8YFLogxK
U2 - 10.1007/s00467-018-4049-5
DO - 10.1007/s00467-018-4049-5
M3 - Article
C2 - 30159624
AN - SCOPUS:85052676249
SN - 0931-041X
VL - 34
SP - 117
EP - 128
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 1
ER -