慢性肾脏病继发性甲旁亢的治疗研究进展

Research Progress in the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease

摘要: 慢性肾脏病(Chronic Kidney Disease, CKD)是全球范围内日益严峻的公共卫生挑战，其并发症不仅加速肾功能的恶化，更显著增加了患者的心血管死亡风险。继发性甲状旁腺功能亢进(Secondary Parathyroidism, SHPT)作为CKD矿物质和骨异常(Chronic Kidney Disease-Mineral and Bone Disorder, CKD-MBD)的核心病理环节，具有发病率高、危害大、治疗难的特点。随着病程的进展，钙磷代谢紊乱、活性维生素D缺乏及FGF23-Klotho轴的失调，共同驱动甲状旁腺细胞的增殖与甲状旁腺激素(Parathyroid Hormone, PTH)的过量分泌，进而导致高转化骨病、血管及软组织钙化等严重后果。文章将围绕药物治疗、外科手术治疗、微创介入治疗及新兴分子靶点四个核心概念展开SHPT治疗领域的最新研究进展。在药物治疗方面，重点分析了从传统磷结合剂到新型拟钙剂的迭代演变及其在解决药物抵抗中的作用；在外科治疗方面，深入探讨了不同甲状旁腺切除术式在复发率与低钙血症风险之间的差异，以及精准影像定位技术的应用；在微创介入领域，系统评估了热消融技术作为手术替代方案的有效性与安全性争议；在新兴靶点方面，聚焦于miRNA及表观遗传学调控在SHPT发病机制中的最新发现及其转化医学前景。最后，文章总结了现有研究在硬终点证据、长期随访数据及个体化治疗标准方面的不足，并为未来的基础研究与临床实践指明了方向。

Abstract: Chronic Kidney Disease (CKD) has become an increasingly severe global public health challenge. Its complications not only accelerate the progression of renal dysfunction, but also significantly increase the risk of cardiovascular mortality in patients. Secondary Hyperparathyroidism (SHPT), a core pathological component of CKD-mineral and bone disorder (CKD-MBD), is characterized by high incidence, serious harmfulness and therapeutic difficulty. As the disease progresses, disorders of calcium-phosphorus metabolism, deficiency of active vitamin D, and dysregulation of the FGF23-Klotho axis synergistically drive the proliferation of parathyroid cells and excessive secretion of Parathyroid Hormone (PTH), which in turn lead to severe consequences such as high-turnover bone disease, vascular and soft tissue calcification. This paper elaborates on the latest research advances in the field of SHPT treatment focusing on four core aspects: pharmacotherapy, surgical treatment, minimally invasive interventional therapy, and emerging molecular targets. In terms of pharmacotherapy, it emphasizes the iterative evolution from traditional phosphate binders to novel calcimimetics and their roles in overcoming drug resistance. For surgical treatment, it deeply discusses the differences in recurrence rates and hypocalcemia risks among various parathyroidectomy procedures, as well as the application of precise imaging localization techniques. In the field of minimally invasive intervention, it systematically evaluates the controversies regarding the efficacy and safety of thermal ablation techniques as alternatives to surgical treatment. Regarding emerging molecular targets, it focuses on the latest discoveries of miRNA and epigenetic regulation in the pathogenesis of SHPT and their translational medicine prospects. Finally, the paper summarizes the limitations of existing studies in terms of hard endpoint evidence, long-term follow-up data, and individualized treatment standards, and points out the directions for future basic research and clinical practice.