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Background. Intermittent smoking is prevalent amongHispanics, but little is known about whether this smoking pattern associates with increased chronic kidney disease (CKD) risk in this population. The objective of the present study is to identify patterns of exposure associated with CKD in US Hispanics. Methods. We used cross-sectional data on 15 410 participants of the Hispanics Community Health Study/the Study of Latinos, a population-based study of individuals aged 18-74 years, recruited in 2008 to 2011 from four US field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA). Smoking exposure was obtained through a questionnaire. CKD was defined by an estimated glomerular filtration rate of <60 mL/min/ 1.73 m² or a urine albumin-to-creatinine ratio of ≥30 mg/g. Results. Approximately 14% of individuals were daily and 7% were intermittent smokers, and 16% were past smokers. There was a significant interaction between smoking status and packyears of exposure (P = 0.0003). In adjusted models, therewas an increased odds of CKD among daily, intermittent and past smokers by pack-years compared with never smokers. The association of intermittent smokers was significant at 10 pack-years [odds ratio (OR) = 1.38, 95% confidence intervals (CI) 1.06, 1.81], whereas for daily smokers this association was observed at 40 pack-years (OR = 1.43, 95% CI 1.09, 1.89). Conclusions. Our findings of increased risk of CKD among Hispanics who are intermittent smokers support screening and smoking cessation interventions targeted to this population for the prevention of CKD. It also suggests novel mechanistic pathways for kidney toxicity that should be further explored in future studies. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) is the most important source of preventable morbidity and mortality in the United States. Recent clinical studies have suggested that, in addition to being a major cardiovascular risk factor, CS promotes the progression of kidney disease. The mechanisms by which CS promotes the progression of chronic kidney disease have not been elucidated. Here we demonstrate for the first time that human mesangial cells (MCs) are endowed with the nicotinic ACh receptors (nAChRs) α4, α5, α7, α2, α3, and α4. Studies performed in other cell types have shown that these nAChRs are ionotropic receptors that function as agonist-regulated Ca2+ channels. Nicotine induced MC proliferation in a dose-dependent manner. At 10-7 M, a concentration found in the plasma of active smokers, nicotine induced MC proliferation (control, 1,328 ± 50 vs. nicotine, 2,761 ± 90 counts/minute (cpm); P < 0.05) and increased the synthesis of fibronectin (50%), a critical matrix component involved in the progression of chronic kidney disease. We and others have shown that, in response to PKC activation, MC synthesize reactive oxygen species (ROS) via NADPH oxidase. In the current studies we demonstrate that PKC inhibition as well as diphenyleneiodonium and apocynin, two inhibitors of NADPH oxidase, prevented the effects of nicotine on MC proliferation and fibronectin production, hence establishing ROS as second messengers of the actions of nicotine. Furthermore, nicotine increased the production of ROS as assessed by 2′,7′-dichlorofluorescein diacetate fluorescence (control, 184.4 ± 26 vs. nicotine, 281.5 ± 26 arbitrary fluorescence units (AFU); n = 5 experiments, P < 0.05). These studies unveil previously unrecognized mechanisms that indict nicotine, a component of CS, as an agent that may accelerate and promote the progression of kidney disease. [ABSTRACT FROM AUTHOR]