The relationship of urinary neutrophil gelatinase-associated lipocalin with renal inflammation in SLE and non-SLE subjects
Date Issued
2010
Date
2010
Author(s)
Yang, Chun-Chen
Abstract
Objective: Lupus nephritis remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and prompt treatment are important to improve the long-term renal survival of lupus nephritis. Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated as a novel biomarker in various acute kidney injuries and chronic kidney diseases. This study hypothesized that 24-hour urinary NGAL excretion can serve as a new predictor for lupus nephritis.
Methods: We enrolled 37 SLE patients, 19 patients with other autoimmune diseases (including 6 SjÖgren’s syndrome, 3 anti-phospholipid syndrome, 2 mixed connective tissue disease, 2 vasculitidies, 1 rheumatoid arthritis and systemic sclerosis overlap, 1 polymyositis, 1 adult-onset Still’s disease, 1 membranous glomerulonephritis, 1 pemphigus and 1 acute urticaria) as the disease control group（DC）, and 12 health volunteers as the normal control group （NC）. The SLE and disease control groups were further subclassified as the active nephritis and non-renal groups, shown as the SLE-nephritis, SLE-non-renal, DC-nephritis and DC-non-renal groups, respectively. Subjects with current infection (especially urinary tract infection) and diabetes mellitus were excluded. Disease activity of SLE patients was assessed by the SLE Disease Activity Index-2000 (SLEDAI-2K). Renal disease activity of all patients was measured by the renal portion of SLEDAI, known as the renal Disease Activity Index (renal DAI). We measured 24-hour urinary excretion of NGAL and other three inflammatory markers, including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay (ELISA) in all study subjects. We analyzed the relationship between 24-hour urinary excretion of inflammatory markers and clinical parameters, with focus on disease activity and kidney involvement.
Results: In all patients, only 24-hour urinary NGAL excretion rather than those of other three measured urinary inflammatory markers was significantly higher in the active nephritis group than in the non-renal (p = 0.001) and normal control groups (p = 0.000). Furthermore, the SLE-nephritis group had significantly higher urinary NGAL excretion than the DC-non-renal group did (p = 0.000) and a tendency of higher urinary NGAL excretion than the SLE-non-renal group did (p = 0.055). In all patients, urinary NGAL excretion was significantly correlated with the renal DAI scores (rs = 0.327, p = 0.022), serum creatinine levels (rs = 0.398, p = 0.003), serum albumin levels (rs = -0.400, p = 0.004), 24-hour Ccr (rs = -0.420, p = 0.017) and 24-hour urine protein (rs = 0.477, p = 0.000). However, when the study population was confined to the SLE patients, urinary NGAL excretion did not correlate with the total SLEDAI scores (rs = 0.055, p = 0.764), extrarenal SLEDAI scores (rs = -0.234, p = 0.196) and renal DAI scores (rs = 0.099, p = 0.578). In a multivariate logistic regression model after adjusting for age and sex, 24-hour urinary NGAL excretion was found to be a significant predictor for active nephritis in all patients (p = 0.017) with an odds ratio (OR) of 1.112 (95% confidence interval (CI): 1.019-1.214). The area under the receiver operating characteristic (ROC) curve of 24-hour urinary NGAL excretion for active nephritis in all patients was 0.793 (p = 0.001), with a 95% CI of 0.660-0.926.
Conclusion: In the present study, 24-hour urinary NGAL excretion was higher in patients with active nephritis than in those without nephritis, and was well correlated with renal disease activity and several renal laboratory parameters, which indicates the potential use of urinary NGAL as a novel biomarker for renal inflammation.
Subjects
Systemic lupus erythematosus
Lupus nephritis
Neutrophil gelatinase-associated lipocalin
Biomarker
Systemic Lupus Erythematosus Disease Activity Index
SDGs
Type
thesis
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