Adult dominant polycystic kidney disease: A prototypical disease for pharmanutrition interventions

IF 2.4 Q3 NUTRITION & DIETETICS
Maria Serena Lonardo , Bruna Guida , Nunzia Cacciapuoti , Mariastella Di Lauro , Mauro Cataldi
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引用次数: 1

Abstract

Background

Adult Dominant Polycystic Kidney Disease (ADPKD) is an inherited disease, associated with the development of liquid-filled cysts in the kidneys and other organs, causing renal failure. Most patients with ADPKD have mutations in either PKD1 or PKD2 genes, which encode for the two components of ion channels located in cilia and endoplasmic reticulum. These mutations cause an increase in intracellular cAMP and activate mTOR, the AMPK pathway and Jak/Stat-dependent gene transcription ultimately leading to enhanced cell proliferation and survival in cyst epithelium and to fluid release in cyst cavities. The aim of the present review is to discuss the main literature evidence suggesting that these pathologically activated transduction pathways can be targeted with an integrated pharmacological and nutritional, pharmanutrition, strategy.

Methods

We interrogated with no limit of publication time, the PubMed and Scopus databases using the following keywords: ADPKD, pharmacological treatment, nutritional intervention, diet, transduction pathways.

Results

In ADPKD, mTOR enhanced activity may be counteracted both with specific drugs, which have intrinsic dose-limiting toxicities, and with time-restricted feeding or ketogenic diets, and these two approaches could, theoretically, synergize. Likewise, cAMP accumulation in the cytoplasm can be counteracted pharmacologically with V2 receptor antagonists or somatostatin analogues and with nutritional interventions such as hypoosmolar diets, with or without high water intake.

Conclusions

Nutritional interventions impinge on the same transduction pathways targeted by drugs currently used or in development for ADPKD. The use of diet intervention in combination with drugs could help lowering drug dose and, consequently, dose-dependent drug toxicity.

成人显性多囊肾病:药物营养干预的典型疾病
成人显性多囊肾病(ADPKD)是一种遗传性疾病,与肾脏和其他器官中充满液体的囊肿的发展有关,导致肾功能衰竭。大多数ADPKD患者有PKD1或PKD2基因突变,这两个基因编码位于纤毛和内质网的离子通道的两个组成部分。这些突变导致细胞内cAMP增加,激活mTOR、AMPK通路和Jak/ stat依赖基因转录,最终导致囊肿上皮细胞增殖和存活增强,并导致囊肿腔内液体释放。本综述的目的是讨论主要的文献证据,表明这些病理激活的转导途径可以通过综合的药理学和营养、药物营养策略来靶向。方法采用ADPKD、药物治疗、营养干预、饮食、转导途径等关键词对PubMed和Scopus数据库进行检索,检索时间不限。结果在ADPKD中,mTOR活性的增强可以通过具有固有剂量限制毒性的特定药物和限时喂养或生酮饮食来抵消,这两种方法在理论上可以协同作用。同样,细胞质中cAMP的积累可以通过V2受体拮抗剂或生长抑素类似物以及低渗饮食等营养干预(无论是否摄入大量水分)在药理学上抵消。结论营养干预与目前使用或正在开发的ADPKD药物所靶向的转导途径相同。饮食干预与药物联合使用有助于降低药物剂量,从而降低剂量依赖性药物毒性。
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
PharmaNutrition
PharmaNutrition Agricultural and Biological Sciences-Food Science
CiteScore
5.70
自引率
3.10%
发文量
33
审稿时长
12 days
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