Serum Folate and All-Cause Mortality is of Non-Linear Relationship Among Population with Chronic Kidney Disease: A Retrospective Cohort Study

Li-Jun Yan,1,* Fei-Ran Zhang,2,* Yu-Ran Zeng,1 Yang Zheng2 1Department of Hemodialysis, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong Province, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang ZhengDepartment of General Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Jinping District, Shantou City, 515041, Guangdong Province, People’s Republic of ChinaTel +86-754-88905256Fax +86-754-88905320Email stenoname@163.comAim: A transition toward high serum folate concentrations has been noticed following the mandatory folate fortification. To explore this further, we studied the relationship between folate and health outcomes in population with chronic kidney disease (CKD).Methods: We retrospectively explored the relationships between serum folate and risk of all-cause death in this population. We analyzed data of 2142 subjects with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999– 2006. Vital status was followed through December 31, 2006.Results: Cox regression was used to estimate hazard ratios (HRs) of mortality for individuals with serum folate in rest quintiles compared with individuals with the fourth quintile. After an average follow-up of 57.4 months with 157 deaths recorded, a reversed J-shaped association was revealed after conducting multivariable adjustment. The mortality rate in population with lower and higher folate levels were 8.29% and 12.67%, respectively, and the corresponding adjusted HRs were 2.41 (95% confidence interval, CI=1.32– 4.40) and 2.10 (1.20– 3.70). Kaplan–Meier curve showed survival benefits for the fourth quintile of serum folate as compared to the first and fifth quintile.Conclusion: Serum folate concentrations may influence all-cause mortality in a non-linear pattern in the CKD population. It is reasonable to recommend periodic surveillance in the CKD population to maintain the serum folate concentration in an appropriate level.Keywords: serum folate, mortality, chronic kidney disease; CKD, National Health and Nutrition Examination Survey; NHANES, cohort study