Maria Serena Lonardo , Bruna Guida , Nunzia Cacciapuoti , Mariastella Di Lauro , Mauro Cataldi
{"title":"成人显性多囊肾病:药物营养干预的典型疾病","authors":"Maria Serena Lonardo , Bruna Guida , Nunzia Cacciapuoti , Mariastella Di Lauro , Mauro Cataldi","doi":"10.1016/j.phanu.2022.100294","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span><span><span>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 </span>PKD1 or PKD2 genes, which encode for the two components of ion channels located in cilia and </span>endoplasmic reticulum<span>. These mutations cause an increase in intracellular cAMP and activate mTOR<span>, the AMPK<span> pathway and Jak/Stat-dependent gene transcription<span> 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, </span></span></span></span></span><em>pharmanutrition</em>, strategy.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p><span>In ADPKD, mTOR enhanced activity may be counteracted both with specific drugs, which have intrinsic dose-limiting toxicities, and with time-restricted feeding or </span>ketogenic diets<span>, and these two approaches could, theoretically, synergize. Likewise, cAMP accumulation in the cytoplasm can be counteracted pharmacologically with V2 receptor<span> antagonists or somatostatin analogues and with nutritional interventions such as hypoosmolar diets, with or without high water intake.</span></span></p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"20 ","pages":"Article 100294"},"PeriodicalIF":2.4000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Adult dominant polycystic kidney disease: A prototypical disease for pharmanutrition interventions\",\"authors\":\"Maria Serena Lonardo , Bruna Guida , Nunzia Cacciapuoti , Mariastella Di Lauro , Mauro Cataldi\",\"doi\":\"10.1016/j.phanu.2022.100294\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span><span><span>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 </span>PKD1 or PKD2 genes, which encode for the two components of ion channels located in cilia and </span>endoplasmic reticulum<span>. These mutations cause an increase in intracellular cAMP and activate mTOR<span>, the AMPK<span> pathway and Jak/Stat-dependent gene transcription<span> 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, </span></span></span></span></span><em>pharmanutrition</em>, strategy.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p><span>In ADPKD, mTOR enhanced activity may be counteracted both with specific drugs, which have intrinsic dose-limiting toxicities, and with time-restricted feeding or </span>ketogenic diets<span>, and these two approaches could, theoretically, synergize. Likewise, cAMP accumulation in the cytoplasm can be counteracted pharmacologically with V2 receptor<span> antagonists or somatostatin analogues and with nutritional interventions such as hypoosmolar diets, with or without high water intake.</span></span></p></div><div><h3>Conclusions</h3><p>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.</p></div>\",\"PeriodicalId\":20049,\"journal\":{\"name\":\"PharmaNutrition\",\"volume\":\"20 \",\"pages\":\"Article 100294\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2022-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PharmaNutrition\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S221343442200007X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PharmaNutrition","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S221343442200007X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
Adult dominant polycystic kidney disease: A prototypical disease for pharmanutrition interventions
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.