SMOKING AS A NOVEL RISK FACTOR IN THE PROGRESSION OF RENAL DISEASE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 吸烟与肾脏疾病的发展密切相关，表现为肾脏疾病、蛋白尿甚至终末期肾脏疾病的进展加快。我们的中心假设是，吸烟通过诱导内皮功能障碍、炎症和氧化应激加速肾脏进展，导致血压升高和肾血流量相对减少，从而诱发肾脏进展。我们将研究50名吸烟者和50名非吸烟者，他们患有不同程度的继发于高血压相关肾病的肾功能不全（血清肌酐2.0-5.0），同时沿着25名吸烟者和25名非吸烟者，肾功能正常。 项目#1将量化吸烟者和非吸烟者的肾脏疾病进展，并确定全身和/或肾脏血流动力学变化是否导致肾功能丧失。 项目#2将研究吸烟诱导的内皮功能障碍在肾脏进展中的作用。 项目#3将确定吸烟诱导的全身和/或肾脏炎症是否与肾脏疾病的更快进展相关。 最终项目#4将研究吸烟诱导的氧化变化在肾脏进展中的作用。

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. There is a strong association of smoking tobacco with the development of renal disease manifested by enhanced progression of renal disease, proteinuria, and even end-stage renal disease. Our central hypothesis is that smoking accelerates renal progression by inducing endothelial dysfunction, inflammation, and oxidative stress leading to an increase in blood pressure and a relative decrease in renal blood flow predisposing to renal progression. We will study 50 smokers and 50 nonsmokers with varying levels of renal dysfunction (serum creatinine 2.0-5.0) secondary to hypertension-associated renal disease along with 25 smokers and 25 nonsmokers with normal renal function. Project #1 will quantify the progression of renal disease in smokers and nonsmokers and determine whether systemic and/or renal hemodynamic changes lead to loss of renal function. Project #2 will investigate the role of smoking-induced endothelial dysfunction in renal progression. Project #3 will determine whether systemic and/or renal inflammation induced by smoking is associated with more rapid progression in renal disease. The final Project #4 will study the role of smoking induced oxidative changes in renal progression.