Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is associated with cardiovascular disease (CVD), which has contributed to an increase in mortality of CKD patients. The onset of CVD often varies by time-of-day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently during early morning. Blood pressure (BP) and heart rate circadian rhythms account for the diurnal variations in CVD. Preservation of normal circadian time structure from the cardiomyocyte level to the whole organ system is essential for cardiovascular health and CVD prevention. Independent risk factors, such as reduced heart rate variability (HRV) and increased BP variability (BPV), are particularly prevalent in patients with CKD. Analysis of HRV is an important clinical tool for characterizing cardiac autonomic status, and reduced HRV has prognostic significance for various types of CVD. Circadian BP rhythms are classified as extreme dipper, dipper, non-dipper or riser. It has been reported that nocturnal riser BP pattern contributes to cardiovascular threats. Previous studies have indicated that the circadian rhythm of serum phosphate in CKD patients is consistent with the general population, with the highest diurnal value observed in the early morning hours, followed by a progressive decrease to the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities have become the main therapeutic target for treating CVD in CKD patients. It has been reported that high levels of serum phosphate are associated with reduced HRV and increased BPV in CKD patients. However, the mechanisms related to interactions between hyperphosphatemia, HRV and BPV have not been fully elucidated. This review focuses on the evidence and discusses the potential mechanisms related to the effects of hyperphosphatemia on HRV and BPV.