#2918 SERUM 25(OH)-VITAMIN D AND 1,25(OH)2 VITAMIN D IN HEMODIALYSIS PATIENTS: FACTORS AFFECTING THEIR CONCENTRATIONS AND THEIR EFFECT ON SURVIVAL
Authors: Ishimura Eiji , Nakatani Shinya , Fujimoto Takao , Higashimoto Kazunari , Kosoku Akihiro , Okuno Senji , Kakiya Ryusuke 
Published: June 2023

Abstract

Background and Aims
In haemodialysis patients, serum levels of vitamin D metabolites, 25-hydroxy-vitamin D (25D), a nutritional status of vitamin D, and 1,25-dihydroxy-vitamin D (1,25D), an active form of vitamin D, are previously reported to be low. In recent years of new CKD-MBD guidelines utilizing calcimimetics, vitamin D receptor agonists (VDRA) and new phosphate binders, relationship between serum 25D, 1,25D concentrations and clinical parameters in haemodialysis patients are not well known. We measured both serum 25D and 1,25D concentrations in chronic haemodialysis patients, and examined their association with several clinical factors and also with survival, in both cross-sectional and longitudinal analyses.

Method
A total of 108 stable haemodialysis patients (72 ± 10 year-old, 64 males, haemodialysis duration 6.9 ± 7.5 years, 45 with type 2 diabetes) were examined. Serum 25D was measured by a ECRIA method, and 1,25D by a RIA2 antibody method, and serum PTH by a IRMA assay. In a cross-sectional analysis, association of these vitamin D metabolites with clinical parameters was examined. In a longitudinal study, patients were followed for 3 years and survival of the patients was examined in relation with these vitamin D metabolites.

Results
Serum 25D concentrations were 12.0 ± 4.0 ng/ml, being hypovitaminosis D (&lt;30 ng/ml) in all patients. Serum 1,25D concentrations were 14.7 ± 8.7 pg/ml, being lower than normal ranges (60-120 pg/ml) in 93% of the patients. There was no significant differences in 25D or 1,25D between those with diabetes and without. Although there was no significant correlation between 25D and haemodialysis duration, there was a significant negative correlation between 1,25D and haemodialysis duration (r = -0.187, p = 0.042). Neither of 1,25D or 25D was significantly correlated with serum calcium or phosphate concentrations. There was a significant, positive correlation between 25D and serum albumin (r = 0.172, p = 0.0454), although there was no significant correlation between 1,25D and serum albumin. Although there was no significant correlation between 25D and serum PTH, there was a significant, negative correlation between 1,25D and serum PTH (r = -0.379, p&lt;0.001). Similarly, although there was no significant correlation between 25D and serum alkaline phosphatase, there was a significant, negative correlation between 1,25D and serum alkaline phosphatase (r = -0.309, p = 0.001). There were no significant differences in serum two vitamin D metabolites between patients with (n = 65) and without VDRA treatment, nor between those with (n = 12) and without calcimimetics. In a multiple regression analysis after adjustment of age, gender, haemodialysis duration, and VDRA treatment, serum 25D concentrations were significantly, independently associated with serum albumin (β = -0.244, p = 0.0149) (R2 = 0.125, p = 0.007). In a multiple regression analysis after the same adjustment, serum 1,25D concentrations were significantly, independently associated with serum intact PTH (β = -0.310, p = 0.003) (R2 = 0.200, p = 0.002). In the follow-up of three year, 16 patients died. Kaplan Meier analysis revealed that there tended to be better survival in patients with higher 25D concentration (n = 52) than those with lower concentration (p = 0.1936), although no significant association was seen between 1,25D and survival.

Conclusion
These results indicate that hypovitaminosis D (low 25D&lt;30 ng/ml) is seen in all haemodialysis patients, and in most of these patients, serum 1,25D concentrations are low. Lower serum 25D concentrations are significantly associated with lower serum albumin, i.e., poorer nutritional status. Higher serum 1,25D, even in low ranges, is significantly associated with lower intact PHT and alkaline phosphatase, i.e. lower bone metabolism status. The results suggest that, in the era of new CKD-MBD treatments with calcimimetics and new VDRA, serum 25D may represent a nutritional status, and that serum 1,25D concentrations with regard to bone metabolism may be re-considered for the assessment of CKD-MBD, particularly in regards to prevention of secondary hyperparathyroidism.