Browsing by Author "Ardoin, Stacy P."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults
    (Wiley, 2016-07) Brunner, Hermine I.; Bennett, Michael R.; Abulaban, Khalid; Klein-Gitelman, Marisa S.; O’Neil, Kathleen M.; Tucker, Lori; Ardoin, Stacy P.; Rouster-Stevens, Kelly A.; Onel, Karen B.; Singer, Nora G.; Eberhard, B. Anne; Jung, Lawrence K.; Imundo, Lisa; Wright, Tracey B.; Witte, David; Rovin, Brad H.; Ying, Jun; Devarajan, Prasad; Medicine, School of Medicine
    OBJECTIVE: 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 histologic LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic 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 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) 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.
  • Thumbnail Image
    Item
    Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein
    (Elsevier, 2014) Ardoin, Stacy P.; Schanberg, Laura Eve; Sandborg, Christy I.; Barnhart, Huiman X.; Evans, Greg W.; Yow, Eric; Mieszkalski, Kelly L.; Ilowite, Norman T.; Eberhard, Anne; Imundo, Lisa F.; Kimura, Yuki; Levy, Deborah; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L.; Punaro, L.; Singer, Nora G.; Sherry, David D.; McCurdy, Deborah K.; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard M.; Wagner-Weiner, Linda; Higgins, Gloria C.; Brunner, Hermine I.; Jung, Lawrence; Soep, Jennifer B.; Reed, Ann M.; Thompson, Susan D.; APPLE investigators; Pediatrics, School of Medicine
    Objective: Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods: Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results: Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions: Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy.