Jennifer L. Asher , Juan B. Ivey-Miranda , Christopher Maulion , Zachary L. Cox , Julian A. Borges-Vela , Genaro H. Mendoza-Zavala , Jose A. Cigarroa-Lopez , Rogelio I. Silva-Rueda , Cristina Revilla-Monsalve , Julieta Moreno-Villagomez , Daniela Ramos-Mastache , Oliver Goedje , Ian Crosbie , Christopher McIntyre , Fredrick Finkelstein , Jeffrey M. Turner , Jeffrey M. Testani , Veena S. Rao
{"title":"一种新型腹腔内糊精/葡萄糖溶液的研制。","authors":"Jennifer L. Asher , Juan B. Ivey-Miranda , Christopher Maulion , Zachary L. Cox , Julian A. Borges-Vela , Genaro H. Mendoza-Zavala , Jose A. Cigarroa-Lopez , Rogelio I. Silva-Rueda , Cristina Revilla-Monsalve , Julieta Moreno-Villagomez , Daniela Ramos-Mastache , Oliver Goedje , Ian Crosbie , Christopher McIntyre , Fredrick Finkelstein , Jeffrey M. Turner , Jeffrey M. Testani , Veena S. Rao","doi":"10.1016/j.xkme.2024.100938","DOIUrl":null,"url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Peritoneal dialysis (PD) solutions provide both clearance of uremic toxins and sodium and water. An intraperitoneal (IP) solution of icodextrin and glucose designed without the requirement for uremic toxin clearance could provide substantially greater sodium and water removal than PD solutions.</div></div><div><h3>Study Design</h3><div>We examined varying concentrations of icodextrin and dextrose IP solutions in rats. We evaluated a 30% icodextrin and 10% dextrose IP solution in animals and humans.</div></div><div><h3>Participants</h3><div>Small and large animal models, and humans (N<!--> <!-->=<!--> <!-->10) with kidney failure.</div></div><div><h3>Exposure</h3><div>30% icodextrin and 10% dextrose IP solution.</div></div><div><h3>Outcomes</h3><div>We evaluated ultrafiltration (UF), sodium removal, and peritoneal health in animals. We evaluated safety, tolerability, and efficacy in humans.</div></div><div><h3>Results</h3><div>In rats, increasing concentrations of icodextrin and dextrose IP solutions, up to 30% icodextrin and 10% dextrose, produced progressively greater UF (<em>P</em> <!--><<!--> <!-->0.001). In sheep treated with 30% icodextrin and 10% dextrose, the mean UF was ∼3.5-fold greater (1.77<!--> <!-->±<!--> <!-->0.22<!--> <!-->L vs 0.47<!--> <!-->±<!--> <!-->0.34<!--> <!-->L; <em>P</em> <!-->=<!--> <!-->0.005) and the mean sodium removal was ∼4-fold greater (7.07<!--> <!-->±<!--> <!-->0.72<!--> <!-->g vs 1.78<!--> <!-->±<!--> <!-->1.27<!--> <!-->g; <em>P</em> <!-->=<!--> <!-->0.003) compared with commercially available 7.5% icodextrin PD solution. Long-term exposure of mice (30 days) and sheep (30-45 days) to a 30% icodextrin and 10% dextrose IP solution resulted in no significant structural tissue changes compared with the control 4.25% commercially available PD solution. In humans, a 24-hour dwell of a 30% icodextrin and 10% dextrose IP solution resulted in median net UF of 2,498<!--> <!-->mL (IQR, 2,249-2,768), and median sodium removal of 387<!--> <!-->mmol (IQR, 372-434<!--> <!-->mmol). No serious adverse events occurred.</div></div><div><h3>Limitations</h3><div>The long-term safety with chronic therapy and the efficacy in patients without kidney failure were not established and require future studies.</div></div><div><h3>Conclusions</h3><div>A 30% icodextrin and 10% dextrose IP solution provides more efficient UF and sodium removal than traditional PD solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div><div><h3>Clinical Trial Registration</h3><div>NCT05780086.</div></div><div><h3>Summary</h3><div>We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div><div><h3>Plain-Language Summary</h3><div>We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"7 1","pages":"Article 100938"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714391/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of a Novel Intraperitoneal Icodextrin/Dextrose Solution for Enhanced Sodium Removal\",\"authors\":\"Jennifer L. Asher , Juan B. Ivey-Miranda , Christopher Maulion , Zachary L. Cox , Julian A. Borges-Vela , Genaro H. Mendoza-Zavala , Jose A. Cigarroa-Lopez , Rogelio I. Silva-Rueda , Cristina Revilla-Monsalve , Julieta Moreno-Villagomez , Daniela Ramos-Mastache , Oliver Goedje , Ian Crosbie , Christopher McIntyre , Fredrick Finkelstein , Jeffrey M. Turner , Jeffrey M. Testani , Veena S. Rao\",\"doi\":\"10.1016/j.xkme.2024.100938\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Rationale & Objective</h3><div>Peritoneal dialysis (PD) solutions provide both clearance of uremic toxins and sodium and water. An intraperitoneal (IP) solution of icodextrin and glucose designed without the requirement for uremic toxin clearance could provide substantially greater sodium and water removal than PD solutions.</div></div><div><h3>Study Design</h3><div>We examined varying concentrations of icodextrin and dextrose IP solutions in rats. We evaluated a 30% icodextrin and 10% dextrose IP solution in animals and humans.</div></div><div><h3>Participants</h3><div>Small and large animal models, and humans (N<!--> <!-->=<!--> <!-->10) with kidney failure.</div></div><div><h3>Exposure</h3><div>30% icodextrin and 10% dextrose IP solution.</div></div><div><h3>Outcomes</h3><div>We evaluated ultrafiltration (UF), sodium removal, and peritoneal health in animals. We evaluated safety, tolerability, and efficacy in humans.</div></div><div><h3>Results</h3><div>In rats, increasing concentrations of icodextrin and dextrose IP solutions, up to 30% icodextrin and 10% dextrose, produced progressively greater UF (<em>P</em> <!--><<!--> <!-->0.001). In sheep treated with 30% icodextrin and 10% dextrose, the mean UF was ∼3.5-fold greater (1.77<!--> <!-->±<!--> <!-->0.22<!--> <!-->L vs 0.47<!--> <!-->±<!--> <!-->0.34<!--> <!-->L; <em>P</em> <!-->=<!--> <!-->0.005) and the mean sodium removal was ∼4-fold greater (7.07<!--> <!-->±<!--> <!-->0.72<!--> <!-->g vs 1.78<!--> <!-->±<!--> <!-->1.27<!--> <!-->g; <em>P</em> <!-->=<!--> <!-->0.003) compared with commercially available 7.5% icodextrin PD solution. Long-term exposure of mice (30 days) and sheep (30-45 days) to a 30% icodextrin and 10% dextrose IP solution resulted in no significant structural tissue changes compared with the control 4.25% commercially available PD solution. In humans, a 24-hour dwell of a 30% icodextrin and 10% dextrose IP solution resulted in median net UF of 2,498<!--> <!-->mL (IQR, 2,249-2,768), and median sodium removal of 387<!--> <!-->mmol (IQR, 372-434<!--> <!-->mmol). No serious adverse events occurred.</div></div><div><h3>Limitations</h3><div>The long-term safety with chronic therapy and the efficacy in patients without kidney failure were not established and require future studies.</div></div><div><h3>Conclusions</h3><div>A 30% icodextrin and 10% dextrose IP solution provides more efficient UF and sodium removal than traditional PD solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div><div><h3>Clinical Trial Registration</h3><div>NCT05780086.</div></div><div><h3>Summary</h3><div>We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div><div><h3>Plain-Language Summary</h3><div>We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.</div></div>\",\"PeriodicalId\":17885,\"journal\":{\"name\":\"Kidney Medicine\",\"volume\":\"7 1\",\"pages\":\"Article 100938\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714391/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590059524001493\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590059524001493","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
理由与目的：腹膜透析（PD）溶液既能清除尿毒症毒素，又能清除钠和水。一种不需要清除尿毒症毒素的卵黄糊精和葡萄糖腹腔内（IP）溶液可以提供比PD溶液更大的钠和水去除效果。研究设计：我们在大鼠体内检测了不同浓度的乙醇糊精和葡萄糖IP溶液。我们在动物和人类中评估了30%的碘糊精和10%的葡萄糖IP溶液。参与者：小型和大型动物模型，以及肾衰竭患者（N = 10）。暴露：30%的乙醇糊精和10%的葡萄糖IP溶液。结果：我们评估了动物的超滤（UF）、钠去除和腹膜健康。我们评估了该药物在人体中的安全性、耐受性和有效性。结果：在大鼠中，增加浓度的icodextrin和葡萄糖IP溶液，高达30%的icodextrin和10%的葡萄糖，产生逐渐增加的UF (P P = 0.005)，平均钠去除率增加约4倍(7.07±0.72 g vs 1.78±1.27 g；P = 0.003)，与市售的7.5% icodextrin PD溶液相比。小鼠（30天）和绵羊（30-45天）长期暴露于30%的碘糊精和10%的葡萄糖IP溶液中，与对照组4.25%的市售PD溶液相比，没有明显的组织结构变化。在人类中，30%的糊精和10%的葡萄糖IP溶液在24小时内停留导致净UF的中位数为2498 mL (IQR, 2249 - 2768)，去除钠的中位数为387 mmol （IQR, 372-434 mmol）。未发生严重不良事件。局限性：慢性治疗的长期安全性和无肾衰竭患者的疗效尚未确定，需要进一步研究。结论：30%的碘糊精和10%的葡萄糖IP溶液比传统的PD溶液更有效地去除UF和钠。有希望的非人道的安全性和有效性结果值得未来的研究，作为一种钠去除治疗患者的水肿疾病，如心力衰竭。临床试验注册：NCT05780086。摘要：我们的目的是设计一种新的腹腔内溶液，以达到最佳的钠和水去除效果。在动物模型和人体中对不含钠的30%糊精和10%葡萄糖腹腔注射溶液进行了评估，以确定其安全性和有效性。30%的乙醇糊精和10%的葡萄糖溶液比传统的腹膜透析溶液更有效地去除钠和水。有希望的非人道的安全性和有效性结果值得未来的研究，作为一种钠去除治疗患者的水肿疾病，如心力衰竭。
Development of a Novel Intraperitoneal Icodextrin/Dextrose Solution for Enhanced Sodium Removal
Rationale & Objective
Peritoneal dialysis (PD) solutions provide both clearance of uremic toxins and sodium and water. An intraperitoneal (IP) solution of icodextrin and glucose designed without the requirement for uremic toxin clearance could provide substantially greater sodium and water removal than PD solutions.
Study Design
We examined varying concentrations of icodextrin and dextrose IP solutions in rats. We evaluated a 30% icodextrin and 10% dextrose IP solution in animals and humans.
Participants
Small and large animal models, and humans (N = 10) with kidney failure.
Exposure
30% icodextrin and 10% dextrose IP solution.
Outcomes
We evaluated ultrafiltration (UF), sodium removal, and peritoneal health in animals. We evaluated safety, tolerability, and efficacy in humans.
Results
In rats, increasing concentrations of icodextrin and dextrose IP solutions, up to 30% icodextrin and 10% dextrose, produced progressively greater UF (P < 0.001). In sheep treated with 30% icodextrin and 10% dextrose, the mean UF was ∼3.5-fold greater (1.77 ± 0.22 L vs 0.47 ± 0.34 L; P = 0.005) and the mean sodium removal was ∼4-fold greater (7.07 ± 0.72 g vs 1.78 ± 1.27 g; P = 0.003) compared with commercially available 7.5% icodextrin PD solution. Long-term exposure of mice (30 days) and sheep (30-45 days) to a 30% icodextrin and 10% dextrose IP solution resulted in no significant structural tissue changes compared with the control 4.25% commercially available PD solution. In humans, a 24-hour dwell of a 30% icodextrin and 10% dextrose IP solution resulted in median net UF of 2,498 mL (IQR, 2,249-2,768), and median sodium removal of 387 mmol (IQR, 372-434 mmol). No serious adverse events occurred.
Limitations
The long-term safety with chronic therapy and the efficacy in patients without kidney failure were not established and require future studies.
Conclusions
A 30% icodextrin and 10% dextrose IP solution provides more efficient UF and sodium removal than traditional PD solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.
Clinical Trial Registration
NCT05780086.
Summary
We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.
Plain-Language Summary
We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.
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