Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-6602, USA.
Lupus. 2012 Mar;21(3):279-87. doi: 10.1177/0961203311425527. Epub 2011 Nov 9.
Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis.
Serum cystatin C, creatinine, tumor necrosis factor (TNF)-α, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models.
Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-α (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99).
Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.
即使是轻度的肾功能损害也与动脉粥样硬化和心血管死亡率的增加有关。胱抑素 C 是一种新型的肾功能指标，比传统的基于肌酐的检测方法更能检测到细微的肾功能损害。胱抑素 C 浓度的升高也与心血管风险相关，独立于传统的肾功能检测方法。本研究检验了这样一个假设，即系统性红斑狼疮（SLE）患者的胱抑素 C 水平升高，并与冠状动脉粥样硬化有关。
测量了 118 例 SLE 患者和 83 例对照者的血清胱抑素 C、肌酐、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、冠状动脉钙评分（CACS）、弗雷明汉风险评分（FRS）、改良肾脏病饮食估计肾小球滤过率（MDRD-eGFR）和其他临床参数。使用多元线性回归模型评估胱抑素 C 浓度与 SLE 之间的独立关联，并使用多元比例优势逻辑回归模型评估肾功能指标与冠状动脉钙之间的关系。
SLE 患者的胱抑素 C 明显高于对照组（1.09 [四分位距，IQR：0.85-1.28] mg/L 比 0.89 [IQR：0.76-0.99] mg/L；调整年龄、种族、性别和 MDRD-eGFR 后，p < 0.001），而其他肾功能指标则无显著差异。胱抑素 C 与 SLICC（p = 0.04）、红细胞沉降率（ESR）（p = 0.02）、TNF-α（p = 0.008）和 IL-6（p = 0.01）显著相关，在调整年龄、种族和性别后。胱抑素 C 与 SLE 患者的冠状动脉钙评分无显著相关性（rho=0.096，p = 0.31），调整年龄、种族、性别和弗雷明汉风险评分后，相关性仍无统计学意义（p = 0.99）。
即使在调整了传统的肾功能指标后，SLE 患者的胱抑素 C 水平仍高于对照组。胱抑素 C 与 SLE 中的几种炎症标志物显著相关，但与冠状动脉粥样硬化无关。轻微的肾功能障碍似乎与 SLE 中加速的动脉粥样硬化没有直接关系。
