Biomarkers Linked to New Onset Proteinuria in Pediatric Lupus Nephritis

The human epidermal growth factor receptor 2 (HER2) and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) biomarkers were associated with new onset proteinuria. Additionally, an increased vascular cell adhesion molecule-1 (VCAM-1) may also predict impending proteinuria. These biomarkers may be useful as potential non-invasive measures for predicting impending flare, according to a study published in Lupus Science and Medicine.¹

“Lupus nephritis is a key driver of morbidity and mortality in systemic lupus erythematosus (SLE),” investigators stated. “Detecting active nephritis on a background of pre-existing renal damage is difficult, leading to potential undertreatment and accumulating injury. An unmet need is a biomarker that distinguishes active lupus nephritis, particularly important in pediatrics where minimizing invasive procedures is desirable.”

This multicenter, prospective study included 113 pediatric patients with biopsy-proven lupus nephritis. Urine samples and other clinical data were collected every 3 to 4 months with an average of 7 time points over a 2-year span. Urine was evaluated for HER2, TWEAK, and VCAM-1 by ELISA. Active disease was defined as either a rise in serum creatine ≥ 0.3 mg/dL from baseline or a rise in the renal Systemic Lupus Erythematosus Disease Activity Index (R-SLEDAI) score when compared with the previous visit. Biomarkers were also assessed in patients with juvenile idiopathic arthritis (JIA), amplified pain syndrome, acute kidney injury, and healthy controls.

The mean age of patients was 15 years, 81% were female, 35% were Black, and 25% were White. The rate of active disease was 56% over the 2-year follow-up period. HER2 and VCAM-1 were significantly higher during times of active disease as defined by an increased serum creatine when compared with patients who did not flare and those with inactive disease. All 3 biomarkers were associated with new-onset proteinuria. VCAM-1 was elevated during the time points preceding new-onset proteinuria.

The longitudinal nature, evaluating diverse racial and ethnic backgrounds, and being the largest prospective assessment within this specific patient population strengthened the study. Additionally, the biomarkers met ideal requirements for the predictive value because they rose alongside an elevation in R-SLEDAI, demonstrating specificity. It should be noted, however, that a single biomarker is not likely to be enough to determine lupus nephritis activity and a combination, comprised of several aspects of pathogenesis, is ideal. Larger studies, identifying biomarkers at the time of flare and before a flare, would be helpful. Further, the samples analyzed for prior visits were comparatively low. More frequent sampling might aid in additional insights regarding the kinetics of these biomarkers. Patients with known lupus nephritis were not included and, therefore, investigators were not able to evaluate the utility of these biomarkers in new-onset cases.

“This prospective pediatric study demonstrates that it is possible to identify biomarkers to predict disease activity in children,” investigators concluded. “Early detection, prior to accumulation of renal damage, is central to improved treatment that minimizes long-term accrual of damage and the evolution of end-stage renal disease.”

Reference:

Costa-Reis P, Maurer K, Petri MA, et al. Urinary HER2, TWEAK and VCAM-1 levels are associated with new-onset proteinuria in paediatric lupus nephritis. Lupus Sci Med. 2022;9(1):e000719. doi:10.1136/lupus-2022-000719