Objectives The renal activity index for lupus (RAIL) measures lupus nephritis (LN) activity considering urine levels of 6 biomarkers (neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, kidney injury molecule-1, adiponectin, haemopexin, ceruloplasmin). We aimed to compare the accuracy of the RAIL and the renal domain-score of the SLE disease activity index (rSLEDAI) in detecting LN activity. Methods Random urine samples of patients with childhood-onset SLE with and without LN were assayed and scores of the RAIL, and RAIL standardised for urine creatinine (RAIL-Cr) were calculated. Clinical LN activity was measured by the rSLEDAI, and histological activity of LN was categorised as inactive/low-moderate/high for National Institute of Health-activity index scores of <2/2–10/>10, respectively. Results 115 patients were included in the analysis (47 patients without and 68 with LN). RAIL, RAIL-Cr and rSLEDAI scores at the time (±3 months) of kidney biopsy were available for 32 patients. Median rSLEDAI, RAIL and RAIL-Cr values were 4, –0.04, 0.02 for inactive LN, 12, 0.7 and 0.9 for low-moderate LN activity and 12, 2 and 1.8 for high LN activity, respectively. The area under the receiver operating characteristic curve (AUC) to capture high LN activity was the lowest for the rSLEDAI (AUC=0.62), followed by the RAIL-Cr (AUC=0.73) and RAIL (AUC=0.79). Notably, when testing urine samples collected during routine clinic visits remote (>3 months) from a kidney biopsy, 50% patients with rSLEDAI scores of 0 had RAIL scores reflecting low-moderate LN activity. Conclusion Monitoring of renal inflammation in children and adolescents with SLE can be improved by the measurement of urine biomarkers. The RAIL may constitute important auxiliary tool for the surveillance of LN in a clinical setting and assist with the decision to obtain a kidney biopsy.

Objective To compare the diagnostic usefulness of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) to that of the 1997 ACR classification criteria for SLE when applied to youths (age <= 21 years) with SLE. Methods Data were extracted from electronic health records of patients followed at a large academic pediatric hospital. The treating rheumatologist's diagnosis of SLE served as the standard criterion for identifying SLE patients (cases). Controls were patients with juvenile dermatomyositis (DM), juvenile scleroderma, or juvenile systemic sclerosis (SSc). The 2019 EULAR/ACR criteria and the 1997 ACR criteria were tested against the standard criterion. Results A total of 112 SLE patients ages 2-21 years and 105 controls ages 1-19 years (66% juvenile DM, 34% juvenile scleroderma or juvenile SSc) were available for analysis. The 2019 EULAR/ACR criteria had significantly higher sensitivity (85% versus 72%; P = 0.023) and similar specificity (83% versus 87%; P = 0.456) than the 1997 ACR criteria. The mean +/- SD 2019 EULAR/ACR classification summary scores were significantly higher among non-White than White patients (22.41 +/- 10.04 versus 17.59 +/- 9.19; P < 0.01). The sensitivity of the 2019 EULAR/ACR criteria in non-White/White patients was 92%/80% (P = 0.08) versus 83%/64% (P < 0.02) for the 1997 ACR criteria. The sensitivity of the 2019 EULAR/ACR criteria was not affected by age or sex. Conclusion The 2019 EULAR/ACR criteria efficiently classify youths with SLE, irrespective of age, sex, and race. Compared to the 1997 ACR criteria, the new criteria are significantly more sensitive and similarly specific in youths with SLE.

OBJECTIVE To compare the diagnostic usefulness of the 2019 European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) to that of the 1997-ACR classification criteria for SLE (1997-ACR) when applied to youths (≤ 21 years) with SLE. METHODS Data were extracted from electronic health records of patients followed at a large academic pediatric hospital. The treating rheumatologist\u0027s diagnosis of SLE served as the standard criterion for identifying SLE patients (cases). Controls were patients with juvenile dermatomyositis (JDM), juvenile scleroderma (jSc) or juvenile systemic sclerosis (jSSc). The 2019-EULAR/ACR criteria and the 1997-ACR criteria were tested against the standard criterion. RESULTS A total of 112 SLE patients aged 2-21 years and 105 controls aged 1-19 years (66% JDM, 34% jSc or jSSc) were available for analysis. The 2019-EULAR/ACR criteria had significantly higher sensitivity (85% vs 72%; p=0.023) and similar specificity (83% vs 87%; p=0.456) than the 1997-ACR criteria. The mean±SD 2019-EULAR/ACR classification summary scores were significantly higher among non-White than White cases (22.41±10.04 vs. 17.59±9.19; p\u003c0.01). The sensitivity of the 2019-EULAR/ACR criteria in non-White/White cases was 92%/80% (p=0.08) vs 83%/64% (p\u003c0.02) for the 1997-ACR criteria. The sensitivity of the 2019-EULAR/ACR criteria was not affected by age or gender. CONCLUSION The 2019-EULAR/ACR criteria efficiently classify youths with SLE, irrespective of age, gender and race. Compared to the 1997-ACR criteria, the new criteria are significantly more sensitive and similarly specific in youths with SLE.

Background Renal involvement in systemic lupus erythematosus (SLE) is associated with high morbidity and mortality. Current standard tools to monitor lupus nephritis (LN) are suboptimal compared to the invasive renal biopsy. The renal activity index in lupus (RAIL) was developed using 6 urinary biomarkers to reflect disease activity. In children this tool was 92% accurate in identifying active LN. We aim to study the changes in this score in relation to induction treatment in LN. Methods Urine samples were collected from active LN patients prior to induction treatment for LN and serially afterwards, coinciding with clinical visits. Luminex Bead Multiplex Assay was used for the analyses of urine biomarkers included in the RAIL score (neutrophil gelatinase-associated lipocalin, ceruloplasmin, monocyte chemoattractant protein-1, adiponectin, hemopexin, kidney injury molecule-1). RAIL scores were calculated per the defined algorithm for each urine sample. Data collected include LN histologic classification (International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification), renal SLE disease activity index (rSLEDAI) score and type of therapy. Results At the time of the analysis, data from 6 active LN patients were collected longitudinally. Patients were all females and all had class IV LN per the ISN/RPS. Renal SLEDAI scores were on the higher end (M=11.3, SD=3.9). All patients were started on intravenous methylprednisolone and cyclophosphamide (CYC) therapy. All but one patient completed 6 doses of monthly CYC before switching to oral mycophenolate mofetil therapy. The RAIL scores for the 6 patients ranged between −1.8 and 3.29. All patients had reductions in their RAIL score at 2–3 months period at an average of 322% decline from baseline (Figure 1). At the end of induction treatment or at the 5–6 months interval, 5/6 samples were available for analysis and showed that 4/5 patients maintained a decline of RAIL scores below the baseline. Of note the patient with higher RAIL score at the end of treatment had only 3 monthly doses of CYC. All rSLEDAI scores decreased between baseline and the 6 months interval. However, one patient with known medication non-adherence had a flare of LN at the 6 months point leading to increased rSLEDAI. Conclusions RAIL scores show overall improvement from baseline with LN induction therapy. Lack of improvement was associated with flare of disease. Additional data points and a larger study sample are required to study the ability of the RAIL score to reflect clinical improvement of LN. Funding Source(s): Academic Research Committee of the Cincinnati Childrens Research Foundation.