Potential Proteinuria Biomarkers in Pediatric LN Identified

A new study has identified 3 biomarkers that may make it easier to identify new-onset proteinuria in pediatric patients with lupus nephritis (LN). The discovery could reduce the need for invasive renal biopsies to track patient renal damage, and the study was published in Lupus Science & Medicine.

LN is common in people with pediatric-onset systemic lupus erythematosus (SLE), with a reported prevalence of 50% to 80%. Many of those patients will progress to end-stage renal disease, which carries with it a significant mortality risk into adulthood.

As more therapies have become available to treat SLE, efforts have proliferated to identify meaningful biomarkers to track patient health and identify the best personalized therapies, the authors noted.

“Urinary biomarkers are particularly attractive as they are not invasive and serial measurements are possible,” they wrote, adding that several markers have been proposed, including ceruloplasmin, angiostatin, CXCL4, vascular cell adhesion molecule-1 (VCAM-1), MCP-1, NGAL, CD11b, HMGB1, hepcidin, and tumor necrosis factor–like weak inducer of apoptosis (TWEAK). “However, thus far there has been little consensus,” the authors said.

In the new study, the investigators sought to identify reliable biomarkers that could distinguish active LN in pediatric patients. They recruited 113 patients with biopsy-proven nephritis and collected urine samples and data every 3 to 4 months for an average of 2 years. Samples were screened for several potential biomarkers, including human epidermal growth receptor 2 (HER2), using enzyme-linked immunosorbent assays.

To isolate active LN, the investigators also studied the same biomarkers in patients with acute kidney injury, juvenile idiopathic arthritis, and amplified pain syndrome, and in healthy controls.

Over the entire study period, the investigators found enrollees with LN had active disease an average of 56% of the time. Further, during periods of active disease, subjects had significantly higher levels of HER2 and VCAM-1 compared with times of inactive disease or in patients with no flares.

HER2, TWEAK, and VCAM-1 were found to be elevated during new-onset proteinuria, and VCAM-1 appeared to be elevated prior to the onset of proteinuria, making it a potential predictive biomarker.

In addition to identifying potential biomarkers, the investigators said their study was important because it highlighted the high rates of active disease among this population.

“This humbling statistic emphasizes the unmet need for improved risk stratification and treatment for pediatric LN,” they said.

The investigators said their findings will require validation in a larger cohort. However, if these results are replicated in a larger cohort, it could enable a paradigm in which point-of-service urine tests can be frequently used to detect proteinuria early and thereby limit renal damage.

“This prospective pediatric study demonstrates that it is possible to identify biomarkers to predict disease activity in children,” they 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