Plasma Fibroblast Growth Factor 23 Levels And Heart Rate Variability In Patients With Stage 5 Chronic Kidney Disease

Objective:Lower heart rate variability(HRV)in patients with chronic kidney disease(CKD)compared with healthy controls is associated with increased risk of cardiovascular disease(CVD).Higher levels of plasma fibroblast growth factor 23(FGF23)also predict higher risk of CVD.Here we aimed to evaluate the relationship between plasma FGF23 levels and HRV in patients with stage 5 CKD and to investigate longitudinal changes of them together with the correlation between their changes in patients with severe secondary hyperparathyroidism(SHPT)who undergone parathyroidectomy(PTX).Methodology:This cross-sectional study included 100 stage 5 CKD patients,78 controls,and a prospective study in two PTX subgroups classified as successful PTX(n = 24)and persistent SHPT(n = 4)follow-up.Clinical characteristics,laboratory results,and 24 hour Holter for HRV were measured.Fasting venous blood were drawn for measuring the levels of plasma C-terminal FGF23(c FGF23)by ELISA.Results:Compared with healthy controls,CKD 5 patients had higher level of plasma c FGF23 [59.0(50.3-77.2)ru/ml vs.6661.4(1226.2-53444.7)ru/ml](P<0.001),most HRV indices were lower in stage 5 CKD patients including mean heart rate(MHR)[(76.4 ± 7.6)beats/min vs.(82.2 ± 11.2)beats/min](P<0.001);mean normal-to-normal R-R intervals(mean NN)[(793.0 ± 77.7)ms vs.(745.5 ±105.6)ms](P=0.001),standard deviation of the normal-to-normal R-Rintervals(SDNN)[(140.1 ± 35.9)ms vs.(78.3 ± 29.7)ms](P<0.001),standard deviation of 5-min average of normal R-R intervals(SDANN)[(127.1±35.1)ms vs.(69.4±28.3)ms](P<0.001),root-mean square of differences between adjacent normal R-R intervals(r MSSD)[(29.9 ± 11.9)ms vs.(19.1 ± 9.5)ms](P<0.001),proportion of adjacent R-R intervals differing by >50 ms over 24-h(p NN50%)[(9.4± 9.3)vs.(3.1 ± 4.9)](P<0.001),very low frequency(VLF)[1017.3(672.7-1588.1)ms2 vs.243.7(132.8-471.1)ms2](P<0.001),low frequency(LF)[180.3(16.9-396.6)ms2 vs.55.9(17.9-148.5)ms2 ](P=0.012),and LF/HF [3.9(2.2-12.1)vs.3.0(1.6-5.8)](P=0.006).In multivariate stepwise regression models,dialysis vintage(P<0.001),levels of serum calcium(P<0.001),phosphorus(P<0.001),alkaline phosphatase(ALP)(P<0.001),and intact parathyroid hormone(i PTH)(P<0.001)were correlated with levels of plasma c FGF23.Levels of i PTH were correlated with mean NN(P=0.001),SDNN(P=0.001),SDANN(P=0.027),p NN50%(P=0.032),and MHR(P=0.002).Also levels of plasma c FGF23 were correlated with SDNN(P=0.008)and SDANN(P=0.001).Levels of ALP were correlated with r MSSD(P=0.015).Twenty-four patients who underwent successful PTX were followed up with an interval of 5 months.Abnormal mineral and bone disorder indices were corrected obviously.Level of serum i PTH decreased from 2129.1(1391.9-3274.7)pg/ml to 99.8(52.88-224.45)pg/ml(P<0.001),serum calcium decreased from(10.1±1.2)mg/dl to(8.5±1.1)mg/dl(P<0.001),serum phosphorus decreased from(7.1±2.5)mg/dl to(3.3±1.8)mg/dl(P<0.001),serum ALP declined from 567.6(370.0-1159.4)?/l to 188.7(103.1-338.1)?/l(P<0.001),and level of plasma c FGF23 reduced from 51558.5(8342.9-118416.2)ru/ml to 4091.5(1766.5-9145.0)ru/ml(P<0.001).Significant changes of HRV indices were observed including MHR(P<0.001),mean NN(P<0.001),SDNN(P=0.003),SDANN(P=0.004),LF(P=0.008),HF(P=0.020),and LF/HF(P=0.008).Fourpatients with persistent SHPT after PTX were also followed-up with an interval of 5 months.Levles of plasma c FGF23 declined obviously after PTX(P=0.021),but there were no significant changes in serum calcium,phosphorus,ALP and i PTH levels.There were no significant differences in HRV indices,even though patients with persistent SHPT shared numerically similar changes with successful PTX patients.Conclusions:Compared with healthy controls,CKD patients had higher levels of plasma c FGF23 and mineral disorder which contributed to the decline of HRV indices.Successful parathyroidectomy may reverse these abnormal indicators and contribute to decreases in the risk of cardiovascular disease.