PowerPoint Slides for: Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease

Background: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. Methods: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). Results: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. Conclusion: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.背景：对于慢性肾脏病（CKD, chronic kidney disease）患者而言，心率变异性（HRV, heart rate variability）降低提示心脏自主神经功能受损，且预示心血管疾病（CVD, cardiovascular disease）发病风险升高。作为慢性肾脏病-矿物质和骨异常（CKD-MBD, CKD-mineral and bone disorder）的临床表现之一，重症继发性甲状旁腺功能亢进症（SHPT, secondary hyperparathyroidism）患者的HRV水平更低，而该异常可通过甲状旁腺切除术（PTX, parathyroidectomy）得到有效逆转。已有研究证实瘦素（leptin）可与自主神经功能产生相互作用，但目前尚不明确CKD患者体内瘦素与HRV之间的关联，以及重症SHPT患者接受PTX治疗后二者的纵向变化情况。 方法：本研究包含两项研究设计：一项针对141例5期CKD患者的横断面研究，以及一项针对36例接受PTX治疗的重症SHPT患者的前瞻性研究。采用动态心电图（Holter）检测HRV，通过酶联免疫吸附试验（ELISA）检测血清瘦素水平。研究对血清瘦素水平进行体重指数（BMI, body mass index）校正，并通过自然对数转换得到lnleptin/BMI指标。 结果：在CKD患者中，随着lnleptin/BMI四分位数从Q1到Q4逐渐升高，各四分位组的HRV指标均未表现出显著统计学差异。Q1组患者的24小时平均心率更高，且极低频率分量对数转换值[ln(very low frequency), lnVLF]低于其余各组，但上述差异未达到统计学显著性水平。在多因素逐步回归分析中，校正BMI后的血清瘦素水平是低频/高频比值（LF/HF）的独立预测因子。重症SHPT患者接受PTX治疗后，其HRV各项指标及lnleptin/BMI水平均有所升高。与其余四分位组相比，Q1组SHPT患者在接受PTX治疗后lnVLF的改善幅度更大。 结论：循环瘦素水平或可作为降低晚期CKD-MBD患者心血管疾病发病风险的新型治疗靶点。