title: Prospective validation of a novel renal activity index of lupus nephritis.
abstract: Objectives The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score >10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.
authors.affiliation: 1 Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, USA.
authors.forename: G
authors.initials: G
authors.lastname: Gulati
authors.affiliation: 2 Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: 3 Division of Pediatric Rheumatology, Helen DeVos Childrens Hospital, USA.|4 Division of Rheumatology, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: K
authors.initials: K
authors.lastname: Abulaban
authors.affiliation: 5 Division of Nephrology, Ohio State University Wexner Medical Center, USA.
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.affiliation: 5 Division of Nephrology, Ohio State University Wexner Medical Center, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 2 Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.affiliation: 6 Department of Pathology, Ohio State University Wexner Medical Center, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Brodsky
authors.affiliation: 6 Department of Pathology, Ohio State University Wexner Medical Center, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nadasdy
authors.affiliation: 2 Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: C
authors.initials: C
authors.lastname: Haffner
authors.affiliation: 4 Division of Rheumatology, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wiley
authors.affiliation: 7 Division of Rheumatology, Ohio State University Wexner Medical Center, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Ardoin
authors.affiliation: 2 Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: P
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: 8 Department of Environmental Health, University of Cincinnati College of Medicine, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ying
authors.affiliation: 5 Division of Nephrology, Ohio State University Wexner Medical Center, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: 4 Division of Rheumatology, Cincinnati Children's Hospital Medical Center, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Brunner
mesh_terms: D052242:Adiponectin / Q000378:metabolism / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D002570:Ceruloplasmin / Q000378:metabolism / Q000652:urine; D018932:Chemokine CCL2 / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006466:Hemopexin / Q000378:metabolism / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D007677:Kidney Function Tests / Q000379:methods; D000071068:Lipocalin-2 / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology* / Q000652:urine*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D018932:Chemokine CCL2; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D006466:Hemopexin; D002570:Ceruloplasmin
keywords: Systemic lupus erythematosus; adult; lupus nephritis; renal activity index of lupus; urinary biomarkers