Prospective validation of a novel renal activity index of lupus nephritis

Abstract

Objectives The Renal Activity Index for Lupus (RAIL) score was developed in children with lupus nephritis (LN) as a weighted sum of six urine biomarkers (RAIL-UBMs) [neutrophil gelatinase associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1] measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with LN. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL-UBMs. Using Receiver Operating Characteristic curve (ROC) analysis, we evaluated the accuracy of the RAIL to discriminate high LN-activity status [National Institutes of Health Activity Index (NIH-AI) score > 10], from low/moderate LN-activity status [NIH-AI score ≤ 10]. Results In this mixed racial cohort, high LN-activity was present in 15 patients (19%), and 71% had proliferative LN. Use of the identical RAIL algorithm developed in children (P-RAIL) resulted only in fair prediction of LN-activity status of adults [area-under the ROC-curve (AUC) 0.62]. Alternative weightings of the six RAIL-UBMs as suggested by logistic regression yielded excellent accuracy to predict LN-activity status (A-RAIL; AUC = 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL-UBMs provide excellent prediction of LN-activity in adults. Age-adaption of the RAIL is warranted to optimize its discriminative validity to non-invasively predict high LN-activity status.

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

“…With the exception of osteopon- tin, these are all validated biomarkers of LN activity and its response to therapy [12, 13, 15, 16]. Accordingly, none of these biomarkers was closely associated with NIH-CI scores in this study.…”

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

“…Urinary KIM-1 was reported to elevated in active LN patients and correlate with renal histological inflammation [ 35 ]. More recently, KIM-1 has been validated as an important component in several different urinary biomarker panels including RAIL for predicting renal pathology [ 36 – 38 ]. In the current study, we also demonstrated that when combined with other UBMs, KIM-1 was able to better reflect renal pathology.…”

“…Urinary NGAL has been validated as a predictor of renal disease activity [ 19 , 39 ], which has been confirmed in the current study. It is also one of the 6 UBMs in RAIL [ 36 , 38 ] that predict renal pathology AI in LN patients. More recently, Satirapoja et al demonstrated that baseline uNGAL performed better than conventional markers in predicting a treatment response in active LN patients with both sensitivity and specificity around 70% [ 20 ].…”

“…Given the complexity of the pathogenesis of lupus nephritis, it is now widely accepted that a single urinary biomarker might not be powerful enough. Many groups have tried different approaches to address this [ 36 , 38 , 43 – 45 ]. In this study, we used a multiplex technology to simultaneously measure 10 candidate UBMs.…”

Clinical trials in children and adolescents with systemic lupus erythematosus: methodological aspects, regulatory landscape and future opportunities

“…More recently, urine biomarkers of lupus nephritis have been discovered and validated for use in children and adults. The Renal Activity Index for Lupus quantifies lupus nephritis activity based on levels of several protein biomarkers measured in the urine 56–58. For capturing joint inflammation with cSLE, the assessment of number of joints with active arthritis and joints with limited range of motion, as done for JIA,59 has face validity.…”