Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Abstract

Background Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. Methods We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs. ≤ 10) or TIAI scores >5 (vs. ≤ 5). RAIL algorithms that predicted LN-activityNIH-AI and LN-activityTIAI status were derived by stepwise multivariate logistical regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. Results The differential excretion of six UBMs (NGAL, MCP-1, ceruloplasmin, adiponectin, hemopexin, KIM-1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activityNIH-AI status with >92% accuracy and LN-activityTIAI status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71 and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. Conclusion The RAIL is a robust and highly accurate noninvasive measure of LN-activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation.

Prospective validation of a novel renal activity index of lupus nephritis

“…The RAIL algorithm proposed for children with LN (P-RAIL) is calculated from the log-transformed and creatinine standardized concentrations of the six RAIL-UBMs as follows: P-RAIL = − 4.29 −0.34* NGAL −0.06*ceruloplasmin + 0.89* MCP-1 + 0.18* adiponectin − 0.65 * hemopexin + 0.62 * KIM-1 (7). The P-RAIL showed outstanding accuracy [area under the receiver operating characteristic curve (AUC) > 0.92] in identifying high LN-activity status (NIH-AI score > 10) in pediatric LN.…”

“…In the development dataset of children, consideration of uncorrected amounts of the RAIL-UBMs in the algorithm mentioned above was less powerful in discriminating LN-activity status (AUC =0.71). Additional details are provided elsewhere (7). …”

“…The six protein urine biomarkers (RAIL-UBMs) are neutrophil gelatinase associated lipocalin (NGAL), monocyte chemotactic protein 1 (MCP-1), ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1 (KIM-1). In children, a RAIL score of 0.39 or higher correctly identified 92% of all children with high LN-activity status, defined as NIH-AI scores exceeding 10 (7). …”

Progression of chronic kidney disease after acute kidney injury

“…114 A number of studies have documented NGAL as a useful measure of CKD in chronic lupus nephritis in children and adults. 115–120 Several additional studies have established the relationship between NGAL and incident CKD in diverse clinical settings, including pediatric heart transplants, 121 adolescents in Nicaragua, 122 and large cohorts of normal subjects including the Multi-Ethnic Study of Atherosclerosis (MESA) cohort 123 and the Atherosclerosis Risk in Communities (ARIC) study. 124 Finally, in the large Chronic Renal Insufficiency Cohort (CRIC) study, urine NGAL levels were independently associated with ischemic atherosclerotic events.…”

A Brief Comment On The Treatment Of Internal Hemorrhoids By Rubber Band Ligation Combined With Sclerotherapy

“…However, this biomarker has a cost burden and doesn't provide additional clinical value over proteinuria. Brunner et [31]. Although these biomarkers seem very promising, further studies are needed to validate its use in LN and determine its added prognostic and diagnostic value to the existing marker "proteinuria".…”