Abstract

Abstract Background and Aims The prevention of chronic kidney disease (CKD) is one of the most important targets all over the world. The harmful effect of smoking was widely reported in patients with CKD, especially in diabetes patients, however, the studies regarding association between smoking and new-onset of CKD in general population has been limited. To clarify this issue, we have collected data from the annual health check-ups on residents in Iki-City (Nagasaki prefecture, Japan), the residents of which show one of the largest morbidity of end-stage kidney disease undergoing dialysis in Japan (3,588 per million), for large-scale cohort study as Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD) Project. In the study reported here, we conducted a retrospective cohort study using 8 years of data obtained from the project to identify the effect of smoking on new-onset of CKD. Method Iki-City is an island which located in the north of Nagasaki prefecture and has approximately 27,000 residents. From 2008 to 2016, a total of 4,540 adults were enrolled into this study. Information on smoking habits was obtained by a self-reported questionnaire. Current smokers were defined as participants who had smoked continuously for more than 6 months at the baseline examination, regardless of the past history of smoking. New-onset CKD was defined as reduction of eGFR down to less than 60mL/min/1.73m2 and/or new-onset proteinuria during the follow-up examinations. Effects of smoking on development of CKD were evaluated using a Cox’s proportional hazards model, and trend in the effects of smoking on outcomes across subgroups defined by age was tested by adding interaction terms to the statistical models. Results The average age of the enrolled residents was 59.6 ± 10.6 years (mean ± SD). During an average follow-up of 4.6 years, CKD was developed in 759 people (36.3 per 1,000 person-years). In the people who developed CKD, proteinuria was developed in 218 people (10.4 per 1,000 person-years) and eGFR decline to less than 60 mL/min/1.73mm2 was confirmed in 594 people (28.3 per 1,000 person-years) including 53 people who showed both proteinuria and eGFR reduction (2.8 per 1,000 person-years). In terms of proteinuria, current smokers showed a higher incidence of 14.1 per 1,000 person-years than non-smoker whose incidence was 9.17 per 1,000 person-years (p=0.001), and a significantly high HR of 1.39 with a 95% CI of 1.01 to 1.92 in multivariable Cox’s proportional-hazards analyses. The incidence of current smokers was almost similar throughout all age, while that of non-smokers increased with their age. (Table 1) The effect of smoking for the incidence of proteinuria was more drastic among younger participants (p=0.015 for trend): younger current smokers (<50 years-old) had a significantly higher HR of 2.55 with a 95% CI of 1.01 to 6.45 (p=0.004) than non-smokers. Conclusion Smoking significantly increased the risk for the new-onset of CKD according to the development of proteinuria in general Japanese population, and the association was more predominate in younger people. From the result of our present study, discontinuing smoking as soon as possible is strongly recommended for all cigarette smokers to prevent CKD.

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