Upcoming drug targets for kidney protective effects in chronic kidney disease
Feb 5, 2025Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Potential new drugs to protect the kidneys in chronic kidney disease
Long-acting (GLP1RA) are recommended for glycemic control in patients with (CKD) and type 2 diabetes.
GLP1RA have been shown to lower the risk of developing end-stage kidney disease.
(ASI) may provide additional benefits when used alongside existing CKD treatments.
Soluble guanylate cyclase (sGC) agonists could help reduce protein in urine by improving nitric oxide bioavailability.
(ERA) may help protect kidneys through their hemodynamic and anti-fibrotic effects.
Emerging clinical trial evidence supports the potential of these therapies to slow the progression of CKD.
AI simplified
UNLABELLED: People with (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as (GLP1RA), (ASi), soluble guanylate cyclase (sGC) and (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.
Key numbers
24%
Reduction in Kidney Failure Incidence
Incidence of primary renal composite endpoint in the FLOW trial.
35%
UACR Reduction
Change in UACR with BI 690517 compared to placebo in a phase 2 trial.
35%
Risk Reduction for ESKD
Reduction in risk of doubling serum creatinine or ESKD in the SONAR trial.
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