Nardone Massimo, Yau Kevin, Kugathasan Luxcia, Odutayo Ayodele, Mohsen Mai, Ouimet Jean-Philippe, Sridhar Vikas S, Cherney David Z I
University Health Network, Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Nephrol Dial Transplant. 2025 Feb 5;40(Supplement_1):i47-i58. doi: 10.1093/ndt/gfae216.
People with chronic kidney disease (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as glucagon-like peptide-1 receptor agonists (GLP1RA), aldosterone synthase inhibitors (ASi), soluble guanylate cyclase (sGC) and endothelin receptor antagonists (ERA), can lower heart-kidney risk in people with CKD. GLP1RA are already recommended for managing blood sugar in people with CKD and type 2 diabetes and have been shown to lower the risk of developing end-stage kidney disease. GLP1RA will likely soon be included in clinical guidelines, but further research is needed to understand how these medications protect the kidneys. ASi are another new medication that lower the protein found in urine. Larger trials are being done to see how well these medications work in slowing CKD. Lastly, both sGC agonists and ERAs have been shown to relax blood vessels to improve blood flow in the kidney, and reduce the amount of protein found in urine, both of which are critical to protecting kidneys. Larger clinical trials are being done to see if these medications prevent CKD from getting worse. In summary, this review describes the new and promising treatments for CKD. These therapies hold the potential to slow kidney disease and improve the wellbeing of patients. Further research of these new treatments is important for improving CKD care.
Despite recent advancements in the treatment of chronic kidney disease (CKD), identifying novel therapies beyond guideline-directed therapies that reduce residual cardiorenal risk remains imperative. In this review, we highlight the clinical evidence supporting emerging therapies for CKD, including glucagon-like peptide-1 receptor agonists (GLP1RA) and other incretin-based therapies, aldosterone synthase inhibitors (ASI), endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) agonists and anti-inflammatory drugs. Long-acting GLP1RA are already recommended for glycemic control in patients with CKD and type 2 diabetes and the large, dedicated kidney outcome trial FLOW was recently stopped early for efficacy. Emerging clinical trial evidence supports the concept that ASI also provide additional benefit on top of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which remain a cornerstone of CKD treatment. Next, we consider the use of sGC agonists, which target nitric oxide bioavailability and thereby reduce albuminuria. Finally, we explore the therapeutic potential of ERA, which act through hemodynamic and anti-fibrotic mechanisms, thereby addressing a common final pathway in the development of CKD. Accordingly, our review highlights the changing therapeutic landscape for CKD with promising agents to further prevent the progression of kidney disease.
慢性肾脏病（CKD）患者患心脏病和终末期肾病的风险很高。本综述描述了新药物，如胰高血糖素样肽-1受体激动剂（GLP1RA）、醛固酮合酶抑制剂（ASi）、可溶性鸟苷酸环化酶（sGC）和内皮素受体拮抗剂（ERA），如何降低CKD患者的心肾风险。GLP1RA已被推荐用于管理CKD合并2型糖尿病患者的血糖，并已显示可降低发生终末期肾病的风险。GLP1RA可能很快会被纳入临床指南，但需要进一步研究以了解这些药物如何保护肾脏。ASi是另一种可降低尿中蛋白质的新药。正在进行更大规模的试验，以观察这些药物在延缓CKD进展方面的效果。最后，sGC激动剂和ERA均已显示可舒张血管以改善肾脏血流，并减少尿中蛋白质含量，这两者对于保护肾脏都至关重要。正在进行更大规模的临床试验，以观察这些药物是否能防止CKD恶化。总之，本综述描述了CKD有前景的新治疗方法。这些疗法有可能延缓肾病进展并改善患者的健康状况。对这些新疗法进行进一步研究对于改善CKD治疗很重要。
尽管慢性肾脏病（CKD）治疗最近取得了进展，但确定除指南指导疗法之外可降低残余心肾风险的新疗法仍然至关重要。在本综述中，我们强调了支持CKD新兴疗法的临床证据，包括胰高血糖素样肽-1受体激动剂（GLP1RA）和其他基于肠促胰岛素的疗法、醛固酮合酶抑制剂（ASI）、内皮素受体拮抗剂（ERA）、可溶性鸟苷酸环化酶（sGC）激动剂和抗炎药物。长效GLP1RA已被推荐用于CKD合并2型糖尿病患者的血糖控制，大型专门的肾脏结局试验FLOW最近因疗效显著而提前终止。新出现的临床试验证据支持这样的概念，即ASI在血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂（它们仍然是CKD治疗的基石）的基础上还能提供额外益处。接下来，我们考虑使用sGC激动剂，其靶向一氧化氮生物利用度，从而减少蛋白尿。最后，我们探讨ERA的治疗潜力，其通过血流动力学和抗纤维化机制发挥作用，从而解决CKD发展中的一个共同最终途径。因此，我们的综述突出了CKD不断变化的治疗格局，有前景的药物可进一步预防肾病进展。
