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Abstract: TH-PO650

7000-Plex Proteomic Screen of Urine for Flare Monitoring and Treatment Response Biomarkers in Active Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Mohan, Chandra, University of Houston, Houston, Texas, United States
  • Vanarsa, Kamala, University of Houston, Houston, Texas, United States
  • Ma, Yewei, University of Houston, Houston, Texas, United States
  • Daouk, Mohammad, University of Houston, Houston, Texas, United States
  • Maruvada, Vinaika, University of Houston, Houston, Texas, United States
  • Saxena, Ramesh, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with lupus. Since the kidney biopsy is invasive, better, more predictive biomarkers of kidney injury are warranted.

Methods

Clarified urine samples from biopsy proven LN patients with differing degrees of disease activity, and healthy controls, were subjected to a 7000-plex aptamer based proteomic screen. The screening cohort included 15 LN patients with active LN, 6 with inactive LN, 9 healthy controls, and 6 LN patients with serial pre-flare and post-flare urine collections, at an average interval of 3 mo.

Results

Compared to inactive lupus, 605 proteins were significantly differentially expressed in active LN urine (Fig. 1A), with 279 proteins elevated >2-fold at ROC AUC≥0.80. Gene enrichment analysis implicated several functional pathways including receptor-mediated endocytosis, regulation of immune response, GTPase activity , among others. Following treatment, post-flare samples compared to flare samples exhibited 2817 proteins significantly reduced ≥50% (Fig. 1B). Comparing renal flare to pre-flare samples. 398 urine proteins were elevated during flare, with ROC AUC >0.90 and WRS test p-≤ 0.125 (Fig. 1A).
A flare response index (FRI) was computed for each urine biomarker, reflecting its fold-change across pre-flare, through flare, to post-flare intervals. Compared to the FRI of urine albumin (6.5), the top 22 urine biomarkers exhibited FRI > 100 (with the highest reaching ~2000).

Conclusion

These studies have identified several novel urine biomarkers of active LN that are highly responsive to renal flares, compared to albuminuria. Further validation studies are warranted.

Figure 1. Heatmap representation of urine proteins differentially expressed in lupus nephritis during renal flares compared to pre-flare (A) and renal flare versus post flare following treatment (B), based on hierarchical clustering.

Funding

  • Other NIH Support