Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease

Purpose

Decreased heart rate variability (HRV) is closely related to abnormal cardiac autonomic nervous function, especially sympathetic hyperactivity, which intensifies the risk of cardiovascular events and sudden death. HRV parameters are lower in chronic kidney disease (CKD) and parathyroidectomy (PTX) can improve these abnormalities in severe secondary hyperparathyroidism (SHPT) patients. However, few studies have evaluated correlations between circulating bone markers and HRV in CKD patients.

Methods

We conducted a cross-sectional study including 134 stage 5 CKD patients with 100 controls and a prospective study of 29 PTX patients with follow-up. Circulating bone biomarkers included: (1) intact parathyroid hormone (iPTH) as bone remodeling regulator; (2) bone-specific alkaline phosphatase (BAP), representing bone formation; (3) tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption; and (4) bone-derived hormone, fibroblast growth factor 23 (FGF23).

Results

Stage 5 CKD patients had higher circulating iPTH, BAP, TRACP-5b, and FGF23 than controls and these bone markers were significantly elevated in SHPT patients. Baseline iPTH, BAP, and lnFGF23 were independently associated with HRV in CKD patients. After PTX with a follow-up (median interval: 6.7 months), high blood iPTH, BAP, TRACP-5b, FGF23, and attenuated HRV were ameliorated. Furthermore, improved HRV indices were associated with reduced iPTH, BAP, TRACP-5b, and FGF23.

Conclusions

Circulating bone markers are correlated with HRV in CKD 5 patients and PTX can improve decreased HRV, which are associated with corrected bone markers in severe SHPT patients. Thus, we propose that PTH increases sympathetic tone and both high circulating PTH levels and sympathetic hyperactivity increase bone turnover, and that the products of bone turnover influence HRV.

     

调整腺嘌呤饮食磷含量制作慢性肾病高磷血症的小鼠模型

目的：通过调整腺嘌呤饮食中的磷水平,建立慢性肾脏病伴高磷血症的小鼠模型。方法：将雄性C57BL/6小鼠分为腺嘌呤饮食组（腺嘌呤0.2%,钙1.0%,磷0.6%）及其对照组（钙1.0%,磷0.6%）、腺嘌呤联合高磷饮食组（腺嘌呤0.2%,钙0.6%,磷1.0%）及其对照组（钙0.8%,磷0.6%）,每组各7只。于造模前、造模4周记录体重,测血尿素氮（BUN）、钙（Ca）、磷（P）水平,4周后取肾脏组织,RT?PCR检测肾纤维化指标包括Ⅰ型胶原蛋白（CollagenⅠ）、纤连蛋白（fibronectin,FN）、纤溶酶原激活物抑制剂?1（plasminogen activator inhibitor?1,PAI?1）以及炎症指标肿瘤坏死因子?α（tumor necrosis factor α,TNF?α）、白细胞介素?1β（interleukin?1β,IL?1β）、细胞间黏附分子?1（intercellular adhesion molecule?1,ICAM?1）等的表达情况。结果：与相应的对照组比,腺嘌呤饮食组4周时体重降低,血BUN明显升高,为（41.15 ± 4.59）mmol/L;Ca、P轻度升高,分别为（2.62 ± 0.16）mmol/L、（2.22 ± 0.26）mmol/L（P < 0.05）。腺嘌呤联合高磷饮食组造模4周时血BUN［（14.68 ± 3.57）mmol/L］轻度升高、P［（2.97 ± 0.29）mmol/L］明显升高（P < 0.05）,血Ca水平无明显差异。RT?PCR显示腺嘌呤饮食组和腺漂呤联合高磷饮食组小鼠肾脏组织中CollagenⅠ、FN、PAI?1、TNF?α、IL?1β、ICAM?1表达水平均较相应对照组升高。结论：腺嘌呤联合高磷饮食饲喂C57BL/6小鼠4周即可建立高磷血症模型,同时伴有轻度肾功能下降、肾脏纤维化,是制备慢性肾脏病伴高磷血症小鼠模型的可行方法。