Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity - PubMed (original) (raw)

. 2009 Sep;60(9):2772-81.

doi: 10.1002/art.24751.

Michiko Suzuki, Marisa Klein-Gitelman, Murray H Passo, Judyann Olson, Nora G Singer, Kathleen A Haines, Karen Onel, Kathleen O'Neil, Earl D Silverman, Lori Tucker, Jun Ying, Prasad Devarajan, Hermine I Brunner

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Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity

Claas H Hinze et al. Arthritis Rheum. 2009 Sep.

Abstract

Objective: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).

Methods: One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.

Results: Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.

Conclusion: Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.

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Figures

Figure 1

Figure 1

Categorization of the Disease Course with childhood-onset SLE (A) The disease course was categorized as persistently active, persistently inactive, improved or worsening. For patients to be categorized as having persistently active (inactive) disease the disease activity score had to remain above (below) a predefined threshold and the change could not exceed a predefined magnitude. If the change exceeded a predefined magnitude, patients were categorized as having improved (if decreased score) or worsening (if increased score) disease activity. (B) The predefined thresholds and required changes are shown. * MD-Global: Physician global assessment score measured on a 10 cm visual analog scale; 0 = inactive SLE. ** MD-Renal: Physician renal assessment score measured on a 10 cm visual analog scale; 0 = inactive SLE renal disease. † SLEDAI-2K-Global/Extrarenal: Systemic Lupus Erythematosus Disease Activity Index 2000 Update global/extrarenal score; range 0 – 105/0–89; 0 = inactive SLE § SLEDAI-2K-Renal: Systemic Lupus Erythematosus Disease Activity Index 2000 Update renal score; range 0 – 16; 0 = inactive SLE renal disease. ‡ BILAG-Global/Extrarenal: British Isle Lupus Assessment Group global/extrarenal score; range 0–72/0–63; 0 = inactive SLE. ¶ BILAG-Renal: British Isle Lupus Assessment Group renal score; range 0–9; 0 = inactive SLE renal disease.

Figure 2

Figure 2

ROC curves of predicting worsening of renal disease activity. The sensitivity, specificity of the predicted probability of worsening, estimated from multivariate logistic regression, are represented, using (A) the SLEDAI-2K-Renal as the external standard (AUC = 0.78) “and (B) the BILAG-Renal as the external standard (AUC = 0.80).

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