Download - A78: Urine Biomarkers Role in Predicting the Future Development of Renal Functional Loss With Lupus Nephritis in Children and Adults

ARTHRITIS & RHEUMATOLOGYVol. 66, No. S3, March 2014, p S111DOI 10.1002/art.38494© 2014, American College of Rheumatology

A78: Urine Biomarkers Role in Predicting theFuture Development of Renal Functional LossWith Lupus Nephritis in Children and Adults

Khalid Abulaban,1 Hermine Brunner,2 Shannen L. Nelson,1 Michael Bennett,1 Jun Ying,3

Huijuan Song,4 Paul Kimmel,5 John Kusek,5 Harold Feldman,6

Vasan Ramachandran,7 and Brad H. Rovin4

Background/Purpose: Lupus nephritis (LN) isfrequently associated with a poor long-term prognosis.Current non-invasive blood and urine tests do not reliablypredict the course of LN. The objective of this studywas to evaluate the performance of candidate urinebiomarkers in predicting future kidney function in adultsand children with LN. The biomarker candidates studieswere liver-type fatty acid binding protein (L-FABP),albumin (Alb), monocyte chemoattractant protein 1(MCP-1), Uromodulin, Transferrin and Hepcidin.

Methods: L-FABP, Alb, MCP-1, Uromodulin,Transferrin and Hepcidin were measured by ELISA inurine from 70 adults and 42 children collected at thetime of enrollment into prospective observational LNcohorts. Urine analytes were normalized to urine creat-inine and logarithmically transformed. The associationof each analyte to renal function loss (RFL), defined asa sustained increase of �25% in serum creatinine (SCr;adults) or a decrease in eGFR of �20% (children), wasdetermined using a fixed effect model after adjusting forthe age group (adult vs. child). In addition, the resultswere confirmed using Wilcoxon Rank Sum tests. Logis-tical models were used to predict the presence of RFLusing each biomarker or a combination of the bio-markers. Biomarker performance in predicting RFL wasassessed as the area under a ROC curve (AUC) corre-sponding to the logistical model.

Results: 13 children and 22 adults had RFLduring the mean follow-up period of 6.1 months and 60months, respectively. Overall patients with RFL showedsignificantly higher levels ALB than those without RFL

(p � 0.05, Table). In addition, the levels of L-FABP,MCP-1, and Transferrin were also marginally higher inRFL (p-values � 0.1). The AUC using the combinationof urine L-FABP, Alb, MCP-1 and Utransferrin was0.66, slightly higher than those using any single bio-marker as the predictor (ranging from 0.52–0.63).

Patienttype Biomarker/Cr$

Renal functionloss$

Preserved renalfunction$

p(Fixed effect

model/Wilcoxon)

N 35 77 –LFABP 1.75 � 1.58 1.17 � 1.62 0.084 / 0.066Albumin 5.58 � 2.31 4.46 � 2.19 0.017 / 0.030MCP-1 5.77 � 1.63 4.89 � 2.45 0.064 / 0.034UROMODULIN 2.04 � 1.30 2.14 � 1.14 0.683 / 0.644UTRANSFERRIN 2.27 � 2.27 1.49 � 1.98 0.073 / 0.070

All patientswith LN

HEPCIDIN 3.85 � 1.15 3.57 � 1.67 0.378 / 0.656


Adults withLN

HEPCIDIN 3.80 � 0.95 3.28 � 1.71 0.197 / 0.368


Childrenwith LN

HEPCIDIN 3.91 � 1.45 4.02 � 1.51 0.830 / 0.803

Conclusion: Urine biomarkers L-FABP, Alb andMCP-1 are likely predictive to RFL. Other biomarkerssuch as Uromodulin,Transferrin and Hepcidin are mark-ers of disease activity, but not predictive of RFL.

Disclosure: K. Abulaban, None; H. Brunner, Novartis, Genentech, MedImmune,EMD Serono, AMS, Pfizer, UCB, Janssen, 5, Genentech and Biogen IDEC Inc., 8;S. L. Nelson, None; M. Bennett, None; J. Ying, None; H. Song, None; P.Kimmel, None; J. Kusek, None; H. Feldman, None; V. Ramachandran, None;B. H. Rovin, None.

1Cincinnati Children’s Hospital Medical Center, Cincinnati,OH, 3University of Cincinnati, Cincinnati, OH, 4Ohio State UniversityMedical Center, Columbus, OH, 5NIDDK, National Institutes ofHealth, Bethesda, MD, 6The University of Pennsylvania, Philadelphia,PA, 7Boston University School of Medicine, Boston, MA.

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