Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Shaarav Ghose, Matthew Satariano, Saichidroopi Korada, Thomas Cahill, Raghav Shah, Rupesh Raina
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Abstract

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of diabetic individuals. Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common co-morbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. SGLT-2 inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.
糖尿病肾病管理的进展:整合创新疗法和靶向药物开发
糖尿病肾病(DKD)是慢性肾病的主要病因,约有 40% 的糖尿病患者会因此患病。随着糖尿病患病率的增加,全球糖尿病肾病病例持续上升,2015 年糖尿病患者估计有 4.15 亿人,预计到 2040 年将达到 6.42 亿人。糖尿病与严重的发病率和死亡率相关,分别占男性和女性慢性肾病死亡总数的 34% 和 36%。常见的并发症包括高血压和与衰老相关的肾小球缺失,使疾病的诊断和进展更加复杂。慢性肾脏病的进展涉及多种机制,包括肾小球内皮细胞功能障碍、炎症和纤维化。针对这些机制的治疗已成为多种治疗药物的基础。肾素-血管紧张素-醛固酮系统(RAAS)阻断剂,特别是血管紧张素受体阻断剂(ARB),可显著减少大蛋白尿。SGLT-2 抑制剂能在控制糖尿病的同时保护肾脏,同时降低心血管事件的发生率。新出现的药物包括 GLP-1 激动剂、抗炎药物(如巴多佐酮)和矿皮质激素受体拮抗剂,这些药物在缓解 DKD 病程进展方面显示出良好的前景。许多新型疗法,包括单克隆抗体 CSL346、Lixudebart 和 tozorakimab、间充质干细胞/间质细胞输注,以及通过 INV-202 进行的大麻素-1 受体反向激动,目前都在临床试验中,为进一步的药物开发提供了机会。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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