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

• Type of Material: Article
• Authors: Hermine I. Brunner, University of Cincinnati; Gaurav Gulati, University of Cincinnati; Marisa S. Klein-Gitelman, Northwestern University; Kelly Rouster Stevens, Emory University; Lori Tucker, British Columbia Children's Hospital; Stacey P. Ardoin, Ohio State University; Karen B. Onel, Weill Cornell Medicine; Rylie Mainville, University of Cincinnati; Jessica Turnier, University of Cincinnati; Pinar Ozge Avar Aydin, University of Cincinnati; David Witte, University of Cincinnati; Bin Huang, University of Cincinnati; Michael R. Bennett, University of Cincinnati; Prasad Devarajan, University of Cincinnati
• Language: English
• Date: 2019-01-01
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, IPNA.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00467-018-4049-5
• Title of Journal or Parent Work: PEDIATRIC NEPHROLOGY
• Volume: 34
• Issue: 1
• Start Page: 117
• End Page: 128
• Grant/Funding Information: 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).
• Keywords: Lupus nephritis; Validation; Children; PLASMA; NEPHRITIS; CHILDREN; Science & Technology; Damage; CLASSIFICATION; Biomarker; DISEASE-ACTIVITY; Life Sciences & Biomedicine; ADIPONECTIN; LIPOCALIN NGAL; DIABETIC-NEPHROPATHY; Pediatrics; OSTEOPONTIN; PROGRESSION; Urology & Nephrology; Chronicity
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

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.