Elevated Serum Gamma-Glutamyltransferase (GGT) Activity and the Development of Chronic Kidney Disease (CKD) in Cigarette Smokers

BACKGROUND: Elevated serum gamma-glutamyltransferase (GGT) is predictive of various cardiovascular (CV) risk factors including chronic kidney disease (CKD). Elevated serum GGT has been recognized in smokers who are likely to develop CKD, but no study has focused on serum GGT and CKD in smokers. OBJECTIVES: The aim of this study was to clarify the associations between cigarette consumption, elevation of serum GGT and the development of proteinuria and CKD. PATIENTS AND METHODS: A retrospective 6-year observational study was conducted on 2,603 male workers aged between 40 and 64 years. Incidences of proteinuria detected by dipstick and CKD defined by proteinuria and/or reduced estimated glomerular filtration rate (eGFR) measured in health check-ups were determined 6 years later for those who had been free of them at baseline. RESULTS: Higher means of serum GGT in smokers than in nonsmokers at baseline, and a higher incidence of elevated serum GGT in smokers than in nonsmokers during the 6-year period were recognized only for alcohol consumers. Incidences of proteinuria and moderate or severe CKD which has a high risk of future renal failure or CV disease were higher in the subjects with greater cigarette consumption or a higher serum GGT level. Multiple logistic regression analyses adjusting for major CV risk factors showed a significant interactive effect between smoking and elevated serum GGT on the development of proteinuria and an additive effect of smoking and serum GGT on the development of high-risk CKD. CONCLUSIONS: Elevation of serum GGT in smokers, to a large extent, depends on the associated alcohol consumption. Elevated GGT in smokers plays at least a partial role in the development of CKD, mainly proteinuria, and the underlying mechanisms remain to be elucidated.