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Abstract Number: 1668

Identification of a Serum Measure of Lupus Nephritis Activity That Detects Molecular Pathways and Mechanisms Implicated in Renal Damage

Mikhail Olferiev1, Dina Greenman2, David Fernandez1, Kerry Merritt1, Kyriakos A. Kirou1 and Mary K. Crow3, 1Hospital for Special Surgery, New York, NY, 2Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY, 3Department of Medicine, Hospital for Special Surgery, New York, NY

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Gene Expression, longitudinal studies, lupus nephritis and proteinuria, SLE

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Session Information

Date: Monday, November 6, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Up to 60% of SLE patients develop renal involvement, and renal injury is an important predictor of mortality in patients with SLE. Kidney biopsy is the gold standard for diagnosis of active lupus nephritis (LN), and active LN is associated with proteinuria, active urinary sediment and/or a rise in serum creatinine. Urine protein/creatinine ratio is often used to monitor LN activity over time, and proteinuria is accepted as the most effective predictor of the long-term outcome of LN. However, none of these measures has proved sufficient for identification and analysis of the biologic events that underlie the development of active LN. We analyzed extensive laboratory and clinical data and blood gene expression data in relation to urine protein to identify an informative measure of LN activity over time.

Methods: Forty-seven LN patients were studied. Clinical and laboratory data were collected for an average (range) of 6 (2-12) years. Longitudinal random urine protein/creatinine ratio data were compared to 72 laboratory and clinical parameters in a linear mixed model. Illumina HT-V4 Bead array data (3-13 time points/patient) were obtained from PBMC of 30 LN patients and compared to proteinuria and serum albumin levels.

Results: In a longitudinal analysis of LN patients, serum albumin was the parameter that was most significantly (negatively) correlated with proteinuria (p<0.00001). In addition, serum albumin correlated significantly with serum calcium, sodium, bilirubin, erythrocyte sedimentation rate (ESR), urine red blood cells (URBC) and urine white blood cells (UWBC) (p<0.05) in a multivariate model. In an analysis of longitudinal PBMC gene transcript data, proteinuria did not correlate with any transcript after correction for multiple testing (FDR 0.05). In contrast, serum albumin correlated with 120 transcripts in PBMC from LN patients. Functional analysis of the obtained genes indicates enrichment of transcripts specifically expressed in neutrophils (e.g., DEFA4, MMP8, MMP9, ELANE, ARG1) and genes related to cell-cycle and DNA-damage pathways (p<0.01).

Conclusion: Proteinuria is an indicator of worsening LN. However, its usefulness as a marker is limited by concurrent urinary tract infections, circadian rhythms, oliguria and other factors. Through study of a longitudinal series of LN samples we demonstrate that serum albumin levels negatively correlate with classical measures of renal involvement, including proteinuria, URBC, and UWBC and might herald a renal flare. Moreover, serum albumin levels identified gene transcripts in blood that may reflect significant molecular mechanisms that contribute to LN flare, allowing novel insights into the pathogenesis of LN.


Disclosure: M. Olferiev, None; D. Greenman, None; D. Fernandez, None; K. Merritt, None; K. A. Kirou, None; M. K. Crow, Biogen, Bristol-Myers Squibb, Johnson and Johnson, Merck, Pfizer, Regeneron, 1,Lupus Research Alliance, 3,Astra-Zeneca, Bayer, Bristol-Myers Squibb, MedImmune, NeoVacs,, 5,Hospital for Special Surgery, 6,New York Chapter Arthritis Foundation, 6.

To cite this abstract in AMA style:

Olferiev M, Greenman D, Fernandez D, Merritt K, Kirou KA, Crow MK. Identification of a Serum Measure of Lupus Nephritis Activity That Detects Molecular Pathways and Mechanisms Implicated in Renal Damage [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/identification-of-a-serum-measure-of-lupus-nephritis-activity-that-detects-molecular-pathways-and-mechanisms-implicated-in-renal-damage/. Accessed .
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