| Hemodialysis (HD) in chronic kidney disease (CKD) patients has been shown to be associated with an accumulation of neurotoxic heavy metals. In addition, many of these patients may also manifest cognitive declines. It has emerged from multiple studies that vitamin D has many beneficial roles, including slowing the progression of CKD, as well as aiding in the amelioration of cognitive decline. The efficacy of this treatment, however, may rely on the polymorphism of the vitamin D receptor (VDR) present. A preliminary study from our laboratory indicated that the detection of autoantibodies against nervous system proteins, suggested biomarkers of neurodegeneration, varied according to VDR polymorphism. Building on this finding, this study investigated the association between blood lead (Pb) and neuroantibody (NAb) titers in HD patients. A high prevalence of NAb, particularly against axonal heavy neurofilament (NF-H), astrocyte glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP), were found to be associated with blood Pb based on HD duration. Stratification based on Bsm1 and Fok1 VDR polymorphism showed a greater prevalence of NAb and blood Pb levels in individuals with dominant alleles; the least prevalent NAb and blood Pb levels were found in those with the recessive alleles. Comparing between Bsm1 and Fok1, significantly higher NAb titers were found with the Bsm1 polymorphism. Together, this data confirms previous findings that VDR polymorphisms with the dominant genotype is associated with greater accumulation of the neurotoxic heavy metal, as well as a greater white matter involvement as indicated by the prevalence of NF-H, GFAP, and MBP titers. In addition to these findings, stratification based on race, age, and the patients' county of residence all produced significant differences. A greater prevalence was found among older Caucasian HD patients living in Saratoga County, New York. These results lend insight into the potential contribution of heavy metal accumulation to neurological involvement, as well as the role of VDR polymorphisms, in CKD and HD patients. Furthermore, this study illustrates that NAb detection may possibly serve as a useful biomarker for monitoring the development of cognitive decline in the future. |
