Search

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., Abstract: 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., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Objective: To investigate the involvement of interleukin (IL)-26 in neuroinflammatory processes in multiple sclerosis (MS), in particular in blood-brain barrier (BBB) integrity., Methods: Expression of IL-26 was measured in serum, CSF, in vitro differentiated T helper (T H ) cell subsets, and postmortem brain tissue of patients with MS and controls by ELISA, quantitative PCR, and immunohistochemistry. Primary human and mouse BBB endothelial cells (ECs) were treated with IL-26 in vitro and assessed for BBB integrity. RNA sequencing was performed on IL-26-treated human BBB ECs. Myelin oligodendrocyte glycoprotein 35-55 experimental autoimmune encephalomyelitis (EAE) mice were injected IP with IL-26. BBB leakage and immune cell infiltration were assessed in the CNS of these mice using immunohistochemistry and flow cytometry., Results: IL-26 expression was induced in T H lymphocytes by T H 17-inducing cytokines and was upregulated in the blood and CSF of patients with MS. CD4 + IL-26 + T lymphocytes were found in perivascular infiltrates in MS brain lesions, and both receptor chains for IL-26 (IL-10R2 and IL-20R1) were detected on BBB ECs in vitro and in situ. In contrast to IL-17 and IL-22, IL-26 promoted integrity and reduced permeability of BBB ECs in vitro and in vivo. In EAE, IL-26 reduced disease severity and proinflammatory lymphocyte infiltration into the CNS, while increasing infiltration of Tregs., Conclusions: Our study demonstrates that although IL-26 is preferentially expressed by T H 17 lymphocytes, it promotes BBB integrity in vitro and in vivo and is protective in chronic EAE, highlighting the functional diversity of cytokines produced by T H 17 lymphocytes., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)