Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease
- 180 Downloads
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.
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).
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.
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.
KeywordsChronic kidney disease-mineral and bone disorder Bone markers Heart rate variability Parathyroidectomy Secondary hyperparathyroidism
The authors would like to thank Qing Ma and Yanyan Pan for the care and management of the patients; Yun Xia, Zhihui Song, Jing Tu and Saijun Yang for assistance with the analysis of heart rate variability. This work was funded by the National Natural Science Foundation of China (81270408, 81570666), International Society of Nephrology (ISN) Clinical Research Program (18-01-0247), Construction Program of Jiangsu Provincial Clinical Research Center Support System (BL2014084), Chinese Society of Nephrology (13030300415), Jiangsu Province Key Medical Personnel Project (RC201162, ZDRCA2016002), and Six Major Talents Summit of Jiangsu Province ([2010-WS-026]).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 9.Yamada S, Inaba M, Kurajoh M et al (2008) Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol 69(2):189–196. https://doi.org/10.1111/j.1365-2265.2008.03187.x CrossRefGoogle Scholar
- 12.Al Salmi I, AlRukhaimi M, AlSahow A et al (2016) Mineral bone disorder and its management among hemodialysis patients in the Gulf Cooperation Council: initial findings from the dialysis outcomes and practice patterns study (2012–2015). Saudi J Kidney Dis Transpl 27(Supplement):62–80. https://doi.org/10.4103/1319-2442.194902 CrossRefPubMedGoogle Scholar
- 15.Kurajoh M, Inaba M, Okuno S et al (2011) Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism. Osteoporos Int 22 (3):923–930. https://doi.org/10.1007/s00198-010-1262-x CrossRefPubMedGoogle Scholar
- 23.Tentori F, Wang M, Bieber BA et al (2015) Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol 10(1):98–109. https://doi.org/10.2215/CJN.12941213 CrossRefPubMedGoogle Scholar
- 32.Connelly K, Collister D, Tangri N (2018) Fracture risk and treatment in chronic kidney disease. Curr Opin Nephrol Hypertens 27(3):221–225Google Scholar