The Association between Homocysteinemia and Mortality in Pre-dialysis CKD patients: A Propensity-Score Matched Analysis Using NHANES-National Death Index Link

Background: Hyperhomocysteinemia (HHcy) is considered a risk factor for cardiovascular disease (CVD) including chronic kidney disease (CKD). In this study, we investigated the association between serum homocysteine (Hcy) level and mortality according to the presence of CKD.Methods: Our study included data of 9,895 participants from the 1996–2016 National Health and Nutrition Examination Surveys (NHANES). Moreover, linked mortality data were included and classified into four groups according to the Hcy level. Multivariable-adjusted Cox proportional hazards models using propensity-score were used to examine dose-response associations between Hcy level and mortality.Results: Of 9,895 participants, 1032 (21.2%) participants were diagnosed with CKD. In a multivariate Cox regression analysis including all participants, Hcy level was associated with all-cause mortality, compared with the 1st quartile in Model 3 (2nd quartile: hazard ratio (HR) 1.751, 95% confidence interval (CI) 1.348-2.274, p<0.001; 3rd quartile: HR 2.220, 95% CI 1.726-2.855, p<0.001; 4th quartile: HR 3.776, 95% CI 2.952-4.830, p<0.001). In the non-CKD group, there was a significant association with all-cause mortality; however, this finding was not observed in the CKD group. The observed pattern was similar after propensity score matching. In the non-CKD group, overall mortality increased in proportion to Hcy concentration (2nd quartile: HR 2.195, 95% CI 1.299-3.709, p = 0.003; 3rd quartile: HR 2.607, 95% CI 1.570-4.332, p<0.001; 4th quartile: HR 3.720, 95% CI 2.254-6.139, p<0.001). However, the risk of all-cause mortality according to the quartile of Hcy level did not increase in the CKD groupConclusion: This study found a correlation between the Hcy level and mortality rate only in the non-CKD group. This altered risk factor patterns may be attributed to protein-energy wasting or chronic inflammation status that is accompanied by CKD.