Urine biomarker score captures response to induction therapy with lupus nephritis

Abstract

Background The Renal Activity Index for Lupus (RAIL) consists of urine protein assessment of neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, monocyte chemotactic protein 1, adiponectin, hemopexin, and ceruloplasmin, which non-invasively identifies lupus nephritis (LN). We aimed to delineate RAIL scores with inactive versus active LN and changes over time with response to LN induction therapy. Methods There were 128 pediatric patients with systemic lupus erythematosus (SLE) and age-matched healthy controls recruited in a prospective case control study, with kidney biopsy confirmation of LN. Laboratory and clinical information was recorded and urine collected at diagnosis and end of induction and during maintenance therapy. Response to therapy was assessed by repeat kidney biopsy or laboratory parameters. Urine was assayed for RAIL biomarkers and the RAIL score calculated. Results Pediatric RAIL (pRAIL) scores from 128 children and young adults with SLE (with/without LN: 70/38) including 25 during LN induction therapy, differentiated clinically active LN from inactive LN or without LN, and controls (all p < 0.0017). pRAIL scores significantly decreased with complete LN remission by 1.07 ± 1.7 (p = 0.03). Conclusions The RAIL biomarkers differentiate LN patients based on activity of kidney disease, with decreases of ≥ 1 in pRAIL scores indicating complete response to induction therapy. Significantly lower RAIL scores in healthy controls and in SLE patients without known LN raise the possibility of subclinical kidney disease. Graphical abstract

Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response

“…These findings align with previous works ( 15 – 17 , 21 ). However, a detailed comparative analysis of follow-up test results is lacking, with only one study reporting that an HPX-inclusive biomarker score could represent the response to induction therapy in patients with LN ( 34 ). Our study revealed a positive correlation between changes in biomarker levels and SLEDAI-2k scores, suggesting a highly promising outcome.…”

Flares in Lupus Nephritis: Risk Factors and Strategies for Their Prevention

“…Treatment of LN should be viewed as a longlasting battle, and patients should be informed upfront about the benefit of maintaining treatment for several years, while of course, accounting for their preferences and needs. We anticipate that intensive research in the field of biomarkers, including plasma [69] and urine [70][71][72][73][74][75][76][77] mediators such as TWEAK, VCAM-1, CD163, and matrix metalloproteinases, will be fruitful and provide novel non-invasive tools to monitor renal disease activity, thus enabling prognostication and treatment tailoring in patients with LN.…”

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach

“…In the study, the RAIL biomarkers could accurately predict response to therapy and propensity towards relapse, highlighting that these biomarkers not only hold diagnostic potential but are also capable of predicting the prognosis. RAIL scores could also distinguish clinically active LN from inactive LN or healthy controls in pediatric patients with SLE and decreased by ≥1 point in patients with complete remission [94]. Importantly, the RAIL score outperformed the rSLEDAI in capturing high LN activity (AUC of 0.79 vs. 0.62, respectively).…”

“…Importantly, the RAIL score outperformed the rSLEDAI in capturing high LN activity (AUC of 0.79 vs. 0.62, respectively). Furthermore, the RAIL score could reveal subclinical/lowmoderate LN activity in patients with an rSLEDAI of 0 who had a kidney biopsy more than 3 months ago [95], underscoring its potential as a method to routinely monitor subclinical kidney disease [94].…”