Background/Purpose: 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, as scored using the renal components of SLEDAI, 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. Heatmaps, gene enrichment analyses and Volcano plots were generated using R. Man Whitney U test or Wilcoxon Rank Sum tests were used for statistical comparisons.

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 (Fig. 1B). Following treatment, post-flare samples compared to flare samples exhibited 2817 proteins significantly reduced ≥50% (Fig. 2). Comparing renal flare to pre-flare samples. 398 urine proteins were elevated during flare, with ROC AUC >0.90 and p-≤ 0.125 (Fig. 2).

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

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/7000-plex-proteomic-screen-of-urine-for-flare-monitoring-and-treatment-response-biomarkers-in-active-lupus-nephritis/