Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults

Brunner, H. I.; Bennett, M. R.; Gulati, G.; Abulaban, K.; Klein-Gitelman, M. S.; Ardoin, S. P.; Tucker, L. B.; Rouster-Stevens, K. A.; Witte, D.; Ying, J.; Devarajan, P.

J Rheumatol. 2017 Jun 18; 44(8):1239-1248

Abstract

OBJECTIVE: To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN). METHODS: Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, alpha-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-beta (TGF-beta), transferrin, and vitamin D binding protein (VDBP). RESULTS: Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-beta (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve >/= 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups. CONCLUSION: Low urine levels of TGF-beta and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.

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