Research On The Interaction Of Secondary Hyperparathyroidism And Fibroblast Growth Factor 23

Objective: To investigate the fibroblast growth factor 23 (FGF23) before and after parathyroidectomy with forearm autotransplantation in maintenance hemodialysis patients with advanced secondary hyperparathyroidism (SHPT) and the cause of parathyroid resistance to FGF23 in SHPT in chronic kidney disease.Methods:1,Twenty-one maintenance hemodialysis patients with advanced SHPT undergoing parathyroidectomy with forearm autotransplantation (PTX) were employed in this study. Serum was obtained from 21 SHPT patients before and after PTX days 3 and levels of serum iFGF23 was detected by means of sandwich enzyme-linked immunosorbent assay (ELISA). To further observe immediately changes of FGF23 after PTX, levels of serum iFGF23 was detected before and in 20 minutes in 12 SHPT patients. In the same time, time-course samples were also obtained from 6 of 21 PTX patients. Levels of serum iFGF23 was detected before and in 20th minutes, third, fifth, seventh day after PTX. Furthermore, the 25(OH)D3,IPTH,calcium, phosphorus, calcium and phosphorus product changes were observed before and after PTX.2,The specimens of parathyroid tissue were taken from 8 patients with PTX. The histological sections were routinely stained with hematoxylin-eosin (HE) .According to HE examinations, the specimens were divided into two types: diffuse type (D- type) and nodular type (N-type).Then the expression of Klotho and FGFR1 were detected by Western blot. 3,Parathyroid cells were gotten from three patients with SHPT undergoing PTX, and were cultured in culture medium. After culture with 24 hours, parathyroid cells were randomly divided into several groups as follows: blank-control group, FGF23 stimulation: FGF23 (0.1μg/ml) stimulation group, FGFR3 antibody + FGF23 stimulation group: According to the recommended concentration of FGFR3,0.5μg/ml and1.0μg/ml anti-FGFR3 and FGF23 (0.1μg/ml) co-stimulated for 0h, 2h, 6h, 12h, 24h, 36h. The concentration of i-PTH in culture medium was evaluated by chemiluminescence enzyme immunoassay. Duplicate wells were determined.Results :1,FGF23 was significantly elevated in SHPT patients. In 21 PTX patients, postoperative FGF23 levels were significantly decreased compared with preoperative levels, and this was followed by a reduction in iPTH levels. In addition, calcium levels, phosphorus levels, and calcium-phosphorus product levels were significantly decreased after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study.2,Nodular type of parathyroid tissue exhibited lower Klotho and FGFR1 expression than diffuse type of parathyroid tissue.3,The administration of recombinant FGF23 0.1ug/ml and FGFR3 antibody 1.0ug/ml together, the level of PTH was decreased at 2h.Conclusions:1,Parathyroid glands may regulate circulating FGF-23 levels in SHPT. Parathyroidectomy was associated with a statistically significant decrease in FGF23 concentrations in the short time. Although the levels of FGF23 were still high, but the decreased of FGF23 after PTX may indicated that the PTH may have effect on the secretion of FGF23. As time went, the levels of FGF23 were increased once again, but the exactly reason for this phenomenon is not clear.2,Nodular type of parathyroid tissue exhibited lower Klotho and FGFR1 expression than diffuse type of parathyroid tissue. These results of this study suggested that the depressed expression of the Klotho–FGFR1 complex in hyperplastic glands may explain, at least in part, the resistance to extremely high FGF23 levels that would be expected to decrease the serum PTH levels.3,The administration of recombinant FGF23 0.1ug/ml and FGFR3 antibody 1.0ug/ml together, the level of PTH was decreased at 2h. These results suggested that over-expression of FGFR3 in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients. Objective: To investigate the magnitude of vitamin D deficiency and the causes of the low vitamin D in CKD patients.Methods: Clinical data of 174 inpatients with CKD was analyzed retrospectively. Level of 25(OH)D₃ in these patients, as well as the levels of fasting blood glucose (FBG), fasting insulin (FINS) and serum C-peptide(CP), serum creatinine (Scr), urea nitrogen (BUN), serum alkaline phosphates(ALP),albumin (Alb), serum calcium (Ca) and blood serum P (P), intact parathyroid hormone (iPTH), C reactive protein (CRP), 24 h urine protein, etc were examined. According to 25(OH)D₃ levels of CKD, patients were divided into three groups: group A 25(OH)D₃<25 nmol/L (n=47), group B 25(OH)D₃ 25-50 nmol/L (n=115) and group C 25(OH)D₃>50 nmol/L (n=12). Correlation between 25(OH)D₃ and parameters was analyzed.Results: In the predialysis patients, the prevalence of vitamin D deficiency (<50 nmol/L) was 93.3%, 24.2% patients of those had severe vitamin D deficiency(<25 nmol/L). In the dialysis patients 95.8% had the vitamin D deficiency, of those, 39.1% had severe vitamin D deficiency. Compared group C, group A and B had significant lower levels of Alb, Ca, and had significant higher levels of proteinuria, Scr (all P<0.05). Compared with group A, group B had significant higher levels of Alb, Ca (all P<0.05). Single factor correlation analysis indicated that serum 25(OH)D₃ was a significantly negative correlation with proteinuria (r=-0.383), Scr(r=-0.284),and CP(r=-0.208) (P<0.01); serum 25(OH)D₃ was significantly positive correlated with Alb (r=0.435) and eGFR (r=0.256) (P<0.01); 25(OH)D₃ was negatively correlated with age, BMI, iPTH, ALP, CRP, FINS, IR, serum 25(OH)D₃ was a negative correlation with insulin sensitive index (ISI),but both of the differences were not significant(P>0.05). Multivariable regression analysis showed that there was positive correlation between 25(OH)D₃ and ALB. 25(OH)D₃ was negatively correlated with proteinuria, Scr and CP.Conclusion: The prevalence of vitamin D insufficiency and deficiency in patients with CKD was quite high. Proteinuria and higher CP might contribute to the pathogenesis of vitamin D insufficiency. Alb, CP and Scr are key factors influencing vitamin D level.