PROGNOSTIC INDICATORS IN LUPUS NEPHRITIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 系统性红斑狼疮(SLE)是一种病因不明的自身免疫性疾病，主要影响女性，有非裔美国人的倾向。肾炎的发展是系统性红斑狼疮的一个显著特征，对发病率和死亡率有很大影响。虽然大多数狼疮患者都有一些肾脏损害，但只有15%-30%的患者在最初诊断时有明显的肾炎。另有15%-30%的SLE患者在病程后期发展为肾炎。目前用来筛查肾炎的方法不能发现早期的“无症状”疾病。肾活检是狼疮性肾炎诊断的金标准。然而，由于其侵入性和重复措施的不切实际，它不适合作为筛查工具。肾炎的治疗选择是有限的，并且与显著的毒性相关。治疗方法复杂，有相当大的、可能危及生命的不良反应。如果有狼疮性肾炎风险的患者能够及早被发现，这可能会允许采用毒性较低的治疗方法，从而有可能避免显性肾脏疾病的发生。因此，有必要开发标志物来筛查“无症状”狼疮性肾炎的存在。我们的目标是确定临床上有用的早期亚临床疾病的标志物。这些标记物也将有助于评估正在进行的治疗的疗效。我们将初步确定选定的生物标志物和肾功能的灵敏测量如何与SLE患者在活检时肾活检所定义的肾炎活动性有关。同时，我们将进行一项纵向研究，检验选定的标志物对肾炎发展的预测价值。我们预计在5年内总共招募450名患者和50名对照。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Systemic Lupus Erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects predominantly women with a predilection for the African-American race. Development of nephritis is a prominent feature in SLE, contributing substantially to morbidity and mortality. Although most patients with lupus have some renal involvement, only 15-30% have overt nephritis at the time of initial diagnosis. A further 15-30% of patients with SLE develop nephritis later in the course of their disease. The methods presently employed to screen for nephritis fail to detect early "silent" disease. Renal biopsy is the gold standard for the diagnosis of lupus nephritis. However, it is not suitable as a screening tool due to its invasive nature and the impracticability of repeated measures. Treatment options for nephritis are limited and associated with significant toxicity. Therapies are complicated by considerable, potentially life threatening adverse effects. If patients at risk of developing lupus nephritis could be identified early, this may allow for less toxic therapies to be employed which could potentially avert the development of overt renal disease. There is thus a need for the development of markers to screen for the presence of "silent" lupus nephritis. Our aim is to identify clinically useful markers of early sub-clinical disease. Such markers will also be helpful for the assessment of the efficacy of ongoing treatment. We will initially establish how selected biological markers and sensitive measurements of renal function relate to activity of nephritis as defined by renal biopsy in patients with SLE at the time of biopsy. In parallel we will conduct a longitudinal study examining the predictive value of the selected markers for the development of nephritis. We anticipate enrolling a total of 450 patients and 50 controls over 5 years.