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钠氢交换体3抑制剂替那帕诺作为慢性肾脏病高磷血症创新疗法的有效性和安全性概况:临床研究的系统评价

Effectivity and safety profile of tenapanor, a sodium-hydrogen exchanger isoform 3 inhibitor, as an innovative treatment for hyperphosphatemia in chronic kidney disease: A systematic review of clinical studies.

作者信息

Suciangto William, Rasyid Haerani, Vicente Anastasya Angelica, Suciangto Winny

机构信息

Department of Medical Doctor Study Program, Faculty of Medicine, Hasanuddin University, Makassar City, South Sulawesi Province, Indonesia.

Division of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar City, South Sulawesi Province, Indonesia.

出版信息

Nefrologia (Engl Ed). 2024 Nov-Dec;44(6):796-806. doi: 10.1016/j.nefroe.2024.11.015.

Abstract

BACKGROUND

Chronic kidney disease (CKD) is a major global health problem. Hyperphosphatemia is frequent in CKD and a reason for increased morbidity and mortality as it generates hyperparathyroidism, high fibroblast growth factor 23 (FGF23), and hypocalcemia. Available hyperphosphatemia therapies still have limitations, including risk of metal overload, cardiovascular calcification, and systemic adverse effects (AEs). Tenapanor is a new hyperphosphatemia treatment in CKD with sodium-hydrogen exchanger isoform 3 (NHE3) inhibition mechanism and low systemic AEs.

OBJECTIVES

Discovering the effectivity and safety of tenapanor as hyperphosphatemia management in CKD.

METHOD

Literature searching is performed by using "pubmed" and "science direct" with "tenapanor", "chronic kidney disease", and "hyperphosphatemia" as keywords. The literatures were selected using PRISMA algorithm version 2020. Literature was screened based on Population, Intervention, Comparison, and Outcome (PICO) criteria which are: CKD patients requiring dialysis as population, tenapanor or its combination with dialysis or phosphate binders as intervention, placebo or other phosphate binders without tenapanor as comparison, and serum phosphate, safety profile, and other pleiotropic benefits related to hyperphosphatemia management as the outcome. The included studies then assessed for risk of bias and qualitatively reviewed.

OUTCOME

Tenapanor was able to reduce serum phosphate, generally in a dose-dependent manner. Tenapanor also suppressed FGF23 and parathyroid hormone, probably due to decreased serum phosphate. The frequent AEs were transient mild-to-moderate diarrhea in a dose-dependent manner. Tenapanor was generally well-tolerated with low systemic AEs due to its non-calcium, metal-free, and low-absorbed properties.

CONCLUSION

Tenapanor is an effective and safe option for hyperphosphatemia management in CKD.

摘要

背景

慢性肾脏病(CKD)是一个主要的全球健康问题。高磷血症在CKD中很常见,是发病率和死亡率增加的一个原因,因为它会引发甲状旁腺功能亢进、高成纤维细胞生长因子23(FGF23)和低钙血症。现有的高磷血症治疗方法仍然存在局限性,包括金属过载、心血管钙化和全身不良反应(AE)的风险。替那帕诺是一种用于治疗CKD患者高磷血症的新型药物,其作用机制是抑制钠氢交换体3(NHE3),且全身不良反应较低。

目的

探索替那帕诺治疗CKD患者高磷血症的有效性和安全性。

方法

以“替那帕诺”、“慢性肾脏病”和“高磷血症”为关键词,通过“PubMed”和“ScienceDirect”进行文献检索。使用2020版PRISMA算法筛选文献。根据人群、干预措施、对照和结局(PICO)标准筛选文献,具体为:需要透析的CKD患者为研究人群;替那帕诺或其与透析或磷结合剂的联合使用为干预措施;安慰剂或不含替那帕诺的其他磷结合剂为对照;血清磷、安全性以及与高磷血症管理相关的其他多效性益处为结局指标。然后对纳入的研究进行偏倚风险评估和定性综述。

结果

替那帕诺能够降低血清磷,一般呈剂量依赖性。替那帕诺还能抑制FGF23和甲状旁腺激素,可能是由于血清磷降低所致。常见的不良反应是呈剂量依赖性的短暂轻至中度腹泻。由于替那帕诺具有非钙、无金属且低吸收的特性,其全身不良反应较低,总体耐受性良好。

结论

替那帕诺是治疗CKD患者高磷血症的一种有效且安全的选择。

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