title: Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults.
abstract: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity.
  
  
  
  We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined.
  
  
  
  The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses.
  
  
  
  The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation.
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Khalid
authors.initials: K
authors.lastname: Abulaban
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Klein-Gitelman
authors.affiliation: Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: O'Neil
authors.affiliation: British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Tucker
authors.affiliation: Ohio State University Wexner Medical Center, Columbus.
authors.forename: Stacy P
authors.initials: SP
authors.lastname: Ardoin
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Rouster-Stevens
authors.affiliation: Comer Children's Hospital, University of Chicago School of Medicine, Chicago, Illinois.
authors.forename: Karen B
authors.initials: KB
authors.lastname: Onel
authors.affiliation: Rainbow Babies and Children's Hospital/Case Medical Center and MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Nora G
authors.initials: NG
authors.lastname: Singer
authors.affiliation: Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park.
authors.forename: B
authors.initials: B
authors.lastname: Anne Eberhard
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Jung
authors.affiliation: Columbia University Medical Center, New York, New York.
authors.forename: Lisa
authors.initials: L
authors.lastname: Imundo
authors.affiliation: University of Texas Southwestern Medical Center, Dallas.
authors.forename: Tracey B
authors.initials: TB
authors.lastname: Wright
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: David
authors.initials: D
authors.lastname: Witte
authors.affiliation: Ohio State University Wexner Medical Center, Columbus.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: University of Cincinnati, Cincinnati, Ohio.
authors.forename: Jun
authors.initials: J
authors.lastname: Ying
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers