Wang F-M, Yu F, Tan Y, Liu G, Zhao M-H
Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, PR China Key laboratory of Renal Disease, Ministry of Health of China, PR China Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education of China, PR China.
Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, PR China Key laboratory of Renal Disease, Ministry of Health of China, PR China Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education of China, PR China
Lupus. 2014 Jun;23(7):655-64. doi: 10.1177/0961203314524291. Epub 2014 Feb 17.
The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis.
Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed.
The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2 ± 14.9 ng/ml, p = 0.006; 57.6 ± 57.5 ng/ml vs. 30.5 ± 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 ± 69.6 ng/ml vs. 40.0 ± 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio = 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis.
Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis.
人肾中结缔组织生长因子mRNA的表达可能是狼疮性肾炎进展的早期标志物。因此,我们推测结缔组织生长因子可能参与系统性红斑狼疮和狼疮性肾炎的发病机制。在本研究中,我们着手调查血清结缔组织生长因子水平与系统性红斑狼疮和狼疮性肾炎患者临床病理特征之间的关联。
采用酶联免疫吸附测定法检测非肾性系统性红斑狼疮患者、经肾活检证实的狼疮性肾炎患者及健康对照者的血清样本中血清结缔组织生长因子水平。进一步分析结缔组织生长因子水平与患者临床病理特征之间的关联。
非肾性系统性红斑狼疮患者和狼疮性肾炎患者的血清结缔组织生长因子水平均显著高于正常对照组(分别为34.14±12.17 ng/ml 与22.8±3.0 ng/ml,p<0.001;44.1±46.8 ng/ml与22.8±3.0 ng/ml,p = 0.035)。非肾性系统性红斑狼疮组与狼疮性肾炎组的血清结缔组织生长因子水平无显著差异(34.14±12.17 ng/ml与44.1±46.8 ng/ml,p = 0.183)。狼疮性肾炎患者出现以下临床表现时,血清结缔组织生长因子水平显著升高,包括贫血(51.3±51.4 ng/ml与23.4±9.7 ng/ml,p<0.001)和急性肾衰竭(85.5±75.0 ng/ml与31.2±21.8 ng/ml,p = 0.002)。IV级患者的血清结缔组织生长因子水平显著高于II级、III级和V级患者(分别为57.6±57.5 ng/ml与18.7±6.4 ng/ml,p = 0.019;57.6±57.5 ng/ml与25.2±14.9 ng/ml,p = 0.006;57.6±57.5 ng/ml与30.5±21.3 ng/ml,p = 0.017)。IV级狼疮性肾炎患者中,既有活动性/慢性病变者的血清结缔组织生长因子水平显著高于仅存在活动性病变者(84.9±69.6 ng/ml与40.0±40.2 ng/ml,p = 0.001);III级和IV级狼疮性肾炎合并患者中,既有活动性/慢性病变者的血清结缔组织生长因子水平也显著高于仅存在活动性病变者(63.3±63.4 ng/ml与38.3±37.9 ng/ml,p = 0.035)。血清结缔组织生长因子水平与估计肾小球滤过率呈负相关(r = -0.46,p<0.001),与间质炎症(r = 0.309,p = 0.002)和间质纤维化(r = 0.287,p = 0.004)呈正相关。单因素分析显示,血清结缔组织生长因子水平是狼疮性肾炎患者血清肌酐翻倍的危险因素(p<0.001,风险比=1.015,95%置信区间1.008 - 1.022)。
狼疮患者的血清结缔组织生长因子水平显著升高,且与狼疮性肾炎患者的慢性肾间质损伤及血清肌酐翻倍相关。