Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor.

IF 2.1 Q2 UROLOGY & NEPHROLOGY
Valeria Cernaro, Elisa Longhitano, Chiara Casuscelli, Luigi Peritore, Domenico Santoro
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Abstract

Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.

慢性肾病中的高磷血症:寻找新的治疗范例和特纳帕诺的作用。
高磷血症是慢性肾脏病治疗过程中的一项重大挑战,对心血管并发症和矿物质骨骼紊乱的发病机制有明显影响。解决高磷血症的传统方法包括限制饮食中的磷酸盐、使用磷酸盐结合剂,以及在终末期肾病患者中采用透析治疗。遗憾的是,这些干预措施往往不足以将磷酸盐水平维持在推荐范围内。此外,常用的药物也难免会引起不良反应,从而限制了处方和治疗的依从性。在这种情况下,人们越来越重视探索新型治疗策略。目前的讨论集中在替那潘诺上,这是一种主要作为钠/氢交换器同工酶 3(NHE3)选择性抑制剂的药剂。其作用机制包括调节紧密连接,从而减少钠的吸收和肠道旁细胞对磷酸盐的通透性。此外,替那帕诺还会下调钠依赖性磷酸盐 2b 转运蛋白(NaPi2b)的表达,从而阻碍磷酸盐的跨细胞转运。临床试验阐明了替那帕诺的疗效和安全性。这些证据表明,高磷血症的治疗模式有可能发生转变。然而,围绕替那帕诺的乐观情绪正在迅速升温,这需要适度的热情,因为进一步的研究仍然不可或缺。当务之急是在临床实践的严苛条件下仔细界定其疗效和安全性。在这篇综述中,我们总结了高磷血症与慢性肾脏病-矿物质骨病之间错综复杂的相互作用,讨论了现有的高磷血症药物干预措施,并探讨了新出现的治疗范例,这些范例为控制慢性肾脏病患者体内磷酸盐水平升高提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.90
自引率
5.00%
发文量
40
审稿时长
16 weeks
期刊介绍: International Journal of Nephrology and Renovascular Disease is an international, peer-reviewed, open-access journal focusing on the pathophysiology of the kidney and vascular supply. Epidemiology, screening, diagnosis, and treatment interventions are covered as well as basic science, biochemical and immunological studies. In particular, emphasis will be given to: -Chronic kidney disease- Complications of renovascular disease- Imaging techniques- Renal hypertension- Renal cancer- Treatment including pharmacological and transplantation- Dialysis and treatment of complications of dialysis and renal disease- Quality of Life- Patient satisfaction and preference- Health economic evaluations. The journal welcomes submitted papers covering original research, basic science, clinical studies, reviews & evaluations, guidelines, expert opinion and commentary, case reports and extended reports. The main focus of the journal will be to publish research and clinical results in humans but preclinical, animal and in vitro studies will be published where they shed light on disease processes and potential new therapies and interventions.
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