Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin.The expression of glomerular podocyte slit diaphragm(PSD)-associated proteins,nephrin and podocin,was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs.Chronic inhibi-tion of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats.This suggested that accumulation of AOPPs promotes proteinuria,possibly via down-regulating the expression of PSD-associated proteins.
YANG Li,LIANG Min,ZHOU QiuGen,XIE Di,LOU AiJu,ZHANG Xun & HOU FanFan Key Laboratory for Organ Failure Research,Division of Nephrology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China.
Background Several studies have shown that coronary stenting reduces the frequency of clinical and angiographic restenosis in patients with mild to moderate renal insufficiency. However, less is known about the long-term benefits of stent use in this population. This study was aimed to determine the impact of coronary stenting on extended （5 years） long-term outcomes of patients with chronic renal insufficiency. Methods The study included 602 consecutive patients who underwent successful percutaneous coronary intervention with stenting. Renal insufficiency was defined as an estimated glomerular filtration rate 〈60 rrd.min-1-｜.73 m-2. The major adverse cardiac events were compared for patients with （n=160） and without （n=442） renal insufficiency. Results After the third year of follow-up, nonfatal myocardial infarction and revascularization rates were significantly increased in patients with renal insufficiency compared with those without renal dysfunction （16.9% vs 7.7%, P=0.001; 29.4% vs 15.8%, P 〈0.001）. In patients who had recurrent cardiovascular events, a significantly higher rate of de novo stenosis revascularization was found in patients with renal insufficiency than without renal insufficiency （57.7% vs 22.7%, P 〈0.001）, while there was no significant difference in target lesion revascularization between the groups （51.9% vs 43.6%, P=0.323）. Multivariate analysis demonstrated an independent impact of the presence of renal insufficiency on the major adverse cardiac events （hazard ratio： 1.488, 95% confidence interval： 1.051-2.106, P=0.025） and de novo stenosis （hazard ratio： 5.505, 95% confidence interval： 2.151-14.090, P 〈0.001）. Conclusions The late major adverse cardiac events, after successful coronary stenting, is increased in patients with an estimated glomerular filtration rate 〈60 ml.min-1.1.73m-2. This might be associated with increased risk of de novo stenosis in this population. Chin Med J 2009; 122（2）： 158-164
Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species （ROS）, plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate （NADPH） oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor , tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products （AOPPs） and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production miaht be a novel strateav for the theraoeutic intervention of varietv of fibrotic kidney disorders.
