Clinical measurement of lupus nephritis activity is inferior to biomarker-based activity assessment using the renal activity index for lupus nephritis in childhood-onset systemic lupus erythematosus

Abstract

ObjectivesThe 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.MethodsRandom 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.Results115 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.ConclusionMonitoring 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.

Urine biomarker score captures response to induction therapy with lupus nephritis

“…In this context, RAIL scores will provide additional support for the biologic relevance of the observed response of LN to a given treatment intervention. Importantly, corrected for treatment response, we have shown consistently in the past that changes in RAIL scores are not influenced by the type of concurrent therapies, including the use of proteinuriasparing agents [12][13][14]40].…”

“…Likewise, the standardized adult RAIL score of − 0.97 or higher correctly identifies older patients with active LN with 86% accuracy [13]. We have also shown that the accuracy of pRAIL scores to identify active LN does not require urine creatinine adjustment, and that scores ≥ 2 are consistent with a NIH Activity Index (NIH-AI) value of 10 or higher, while pRAIL scores of 0 or less are consistent with NIH-AI values of 2 or less [14]. RAIL scores decrease (or improve) with immunosuppressive therapy in those with treatment response [11,12].…”

“…We had previously shown that both absolute and standardized pRAIL scores were similarly well suited to discriminate moderate to highly active LN (NIH-AI > 10) from LN with lesser degrees of inflammation as seen on kidney biopsy [11,14]. Using current standard clinical measures of LN, pRAIL scores clearly differentiate active from inactive LN [11,14].…”

“…Prior to use in the RAIL algorithm, biomarker concentrations were natural-log transformed. The pRAIL algorithm was used only for pediatric and young adult cSLE patients up to age 23 years at enrollment, as previously published [13,14]. The pRAIL we evaluated produced standardized and non-standardized scores [13,14].…”

“…The pRAIL algorithm was used only for pediatric and young adult cSLE patients up to age 23 years at enrollment, as previously published [13,14]. The pRAIL we evaluated produced standardized and non-standardized scores [13,14]. The standardized RAIL score refers to the score that utilized creatinine standardized urinary biomarkers, while the nonstandardized score used absolute values of the urinary biomarkers.…”