The strength of the association between smoking and the development of chronic kidney disease (CKD) in the healthy middle-aged working age population has not been established.

This was a retrospective 6-year observational study involving 4,121 male and 2,877 female workers who were free of primary kidney disease, diabetes mellitus, severe hypertension, and the signs and symptoms of CKD. Proteinuria was detected by a dipstick method, and glomerular filtration rate (GFR) was estimated by the equation of the Japan Society of Nephrology.

Sixty men (1.5 %) and 21 women (0.7 %) developed proteinuria over the 6 years of the study. Irrespective of sex, in comparison with non-smokers, those who continued smoking showed an odds ratio (OR) of 2.52 with a 95 % confidence interval (CI) of 1.50–4.25 for developing proteinuria while those who quit smoking showed an OR of 1.29 (95 % CI 0.48–3.42), following adjustment for confounders. Among the study population, 443 men (10.7 %) and 356 women (12.4 %) developed a GFR of 2, corresponding to stage III CKD. Continuing smokers had a low OR (0.74, 95 % CI 0.60–0.90) for developing a low GFR, as well as a higher mean GFR than non-smokers. The reduction in GFR during the 6-year study period was not different between smokers and non-smokers, but it was larger in those who developed proteinuria than in those who did not, irrespective of smoking.

Continuing smokers showed a twofold or more higher risk of developing proteinuria. Discontinuation of smoking substantially reduced the risk. A longer observational period may be required to detect the smoking-induced risk of developing stage III CKD in the middle-aged working population.