ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1304

Development of an Index to Non-Invasively Quantify Lupus Nephritis Chronicity in Children

Khalid Abulaban1, Michael Bennett2, Marisa Klein-Gitelman3, Stacy P. Ardoin4, Kelly A. Rouster-Stevens5, Lori B. Tucker6, Kasha Wiley7, Shannen Nelson8, Karen Onel9, Nora G. Singer10, Kathleen M. O'Neil11, B Anne Eberhard12, Lawrence K. Jung13, Lisa F. Imundo14, Tracey Wright15, David Witte16, Jun Ying17, Prasad Devarajan2 and Hermine I. Brunner18, 1Pediatric Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 3Anne & Robert H Lurie Childrens Hospital of Chicago, Chicago, IL, 4Pediatric & Adult Rheumatology, Ohio State University College of Medicine, Columbus, OH, 5Pediatrics, Emory University School of Medicine, Atlanta, GA, 6Rheumatology, BC Children's Hospital and University of British Columbia, Vancouver, BC, Canada, 7Rheumatology, Cincinnati Children's Hospital Medical Center, c, OH, 8Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 9Pediatric Rheumatology, University of Chicago Hospitals, Chicago, IL, 10Medicine, Division of Rhuematology, Division of Rheumatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, 11Division of Pediatric Rheumatology, Riley Hospital for Children, Indianapolis, IN, 12Pediatrics/Rheumatology, Cohen Children's Medical Center, Lake Success, NY, 13Pediatric Rheumatology, Children's National Medical Center, Washington, DC, 14Assoociate Professor of Pediatrics in Medicine - Rheumatoology, Columbia University Medical Center, New York, NY, 15Pediatrics/Rheumatology, UT Southwestern Medical Center, Dallas, TX, 16Rheumatology, Cincinnati Children's Hospital, Cincinnati, OH, 17University of Cincinnati, Cincinnati, OH, 18Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects: Pediatric Lupus, Scleroderma and Myositis (ACR)

Session Type: Abstract Submissions (ACR)

Background/Purpose: The current gold standard for assessing chronic changes in Lupus Nephritis (LN) is a kidney biopsy interpreted using the International Societies for Nephrology & Renal Pathology (ISN/RPS) Classification. However, kidney biopsies are invasive, costly and unsuited for close surveillance of LN. The objective of this study was to develop a non-invasive Index to measure LN chronicity or damage, considering both traditional measures of LN (LN-TM) and recently discovered renal biomarkers (RBM).

Methods: In this ongoing prospective study, 70 children with LN were studied at the time of the kidney biopsy for the LN-TM [GFR, anti-dsDNA antibodies, urinary protein/creatinine ratio] and the urine concentrations of the RBM (see Table 1) were measured. Histological findings were rated by a single nephropathologist who provided the NIH chronicity index (NIH CI; range 0-12) which served as the Criterion Standard. Prior to statistical analysis, RBM levels were normalized by urine creatinine and logarithmically transformed. NIH-CI scores ranged from 0 to 12. LN damage was categorized as low (NIH-CI <3) or moderate (NIH-CI >3). LN-TM and the RBM that showed significance in univariate logistic analysis at a p-value<0.20 were considered in exploratory stepwise multivariate logistical regression models as candidate predictors, using the NIH CI as dependent variable (outcome) to assess the combinatorial character of the candidate predictors.

Results: The means and percentages of the values of the LN-TM and RBM levels are summarized (Table1). Based on multivariate logistical regression modeling levels of TGFB, NGAL and GFR (or serum creatinine) but not protein excretion (urinary protein/creatinine ratio) were found to be combinatorial biomarkers of LN damage.  Results on the RBM liver-type fatty acid binding protein (LFABP), Kidney Injury Molecule-1 (KIM1) and the receiver operating characteristic curve analyses will be presented.

Conclusion:  NGAL, TGBF and GFR are good potential components for Children a Lupus Nephritis Index for Damage (C-LID) to non-invasively measure chronic histological changes in LN in the glomeruli, interstitium and tubules.  Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.

  

 

Table1 Comparisons of LN biomarkers between NIH CI Groups

 

 

LN biomarkers

NIH CI Score

 

 

< 3

≥ 3

p

 

 

Protein/ Cr ratio*

1.85 (1.32, 2.59)

3.73 (1.94, 7.18)

0.065

 

 

GFR*

104.39 (90.12, 120.91)

72.00 (54.34, 95.40)

0.025

 

 

Serum Cr*

0.71 (0.62, 0.81)

1.04 (0.80, 1.35)

0.012

 

 

NGAL

0.33 (0.21, 0.53)

0.83 (0.33, 2.08)

0.089

 

 

CP

175 (102, 301)

302 (104, 876)

0.377

 

 

MCP1

11.37 (7.22, 17.90)

10.86 (4.45, 26.49)

0.930

 

 

AGP

929 (416, 2,075)

395 (102, 1,534)

0.298

 

 

TGFB*†

0.69 (0.49, 0.96)

3.37 (1.41, 8.06)

0.005

 

 

ADI

0.17 (0.07, 0.42)

0.29 (0.05, 1.64)

0.591

 

 

HEPCIDIN

0.62 (0.33, 1.17)

0.47 (0.14, 1.56)

0.695

 

 

LPGDS

3.76 (2.30, 6.15)

3.92 (1.49, 10.30)

0.942

 

 

TF

0.12 (0.07, 0.18)

0.17 (0.07, 0.43)

0.470

 

 

VDBP

6.20 (2.94, 13.06)

4.98 (1.15, 21.54)

0.796

 

 

HPX

26.57 (15.11, 46.72)

20.24 (7.12, 57.57)

0.657

 

 

*: Values in the cells are mean (95% CI);
**: Values in the cells are %;
†: N=16, too small sample size for Step 2 analysis.

 

NGAL: neutrophil gelatinase associated lipocalin, MCP1: monocyte chemoattractant protein-1, CP: ceruloplasmin, AGP: alpha1-acid glycoprotein, TF: transferrin, LPDGS: lipocalin-like prostaglandin-D Synthase, ADI: adiponectin, HPX: hemopexin, TGFB: TGF-beta, VDBP: vitamin D binding protein.

 

Disclosure:

K. Abulaban,
None;

M. Bennett,
None;

M. Klein-Gitelman,
None;

S. P. Ardoin,
None;

K. A. Rouster-Stevens,
None;

L. B. Tucker,
None;

K. Wiley,
None;

S. Nelson,
None;

K. Onel,
None;

N. G. Singer,
None;

K. M. O’Neil,
None;

B. A. Eberhard,
None;

L. K. Jung,
None;

L. F. Imundo,
None;

T. Wright,
None;

D. Witte,
None;

J. Ying,
None;

P. Devarajan,
None;

H. I. Brunner,

TMA and NIEHS,

9.

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