Background: Exposure of cigarette smoke and genetic factors, IGF- 1 gene polymorphism, are believed to affect the incidence of end stage renal disease (ESRD). But until now which is more influential on ESRD events, whether external factors, exposure of cigarette smoke or internal factors, IGF-1 gene polymorphism are unknown. Objective: The purpose of this study is to find out which one has more influence on the incidence ESRD whether external factors (exposure of cigarette smoke) or internal factors (IGF-1 gene polymorphisms). Method: It was done by academic literature reviews on the latest academic obtained from primary and secondary literature sources, journals, thesis or dissertation. The data and information are analized and synthesized, be used to answer the problem. The results of the study are presented in descriptive narrative and analytical. Results: The results showed that exposure to both external factors and internal factors, cigarettes smoke, IGF-1 gene polymorphisms, affect the ESRD incidence. Results of observational studies showed that the incidence of smoking increases the risk of ESRD. Data results of case-control studies of IGF- 1 gene polymorphism are also showing that an IGF-1 also increased the incidence of ESRD. Data analysis of interaction between cigarette smoke exposure with IGF-1 gene polymorphisms on the incidence ESRD showed that the effect of cigarette smoke exposure is greater than the effect of IGF-1 gene polymorphisms. Conclusions: the effect of smoke exposure on the incidence ESRD greater than IGF-1 gene polymorphisms.