Pharmacol Res. 2026 Aug 30:108425. doi: 10.1016/j.phrs.2026.108425. Online ahead of print.
ABSTRACT
Kidney transplantation (KT) remains the optimal treatment for kidney failure, improving survival and quality of life. However, long-term graft outcomes have plateaued, largely due to transplant CKD and cardiovascular disease; agents such as mineralocorticoid receptor antagonists (MRAs) may help mitigate these risks. Mineralocorticoid receptor (MR) overactivation contributes to oxidative stress, inflammation, and fibrosis in both the heart and kidneys, suggesting a potential role for mineralocorticoid receptor antagonists (MRAs) in improving long-term patient and graft outcomes. Although evidence in KT is limited, MR blockade may offer clinical benefits by targeting aldosterone-mediated pathways. Proteinuria promotes sodium reabsorption in the aldosterone-sensitive distal nephron via epithelial sodium channels (ENaC), contributing to hypertension and volume overload. MRAs have been shown to reduce albuminuria and blood pressure in patients with diabetic nephropathy, even on background renin-angiotensin-aldosterone system (RAAS) blockade. The use of MRAs post-KT should be individualized, considering patient comorbidities and concomitant immunosuppressive therapy. While MRAs may provide cardiovascular and antiproteinuric benefits, the risk of hyperkalemia-though reduced with non-steroidal MRAs-must be carefully managed. PLAIN LANGUAGE SUMMARY: When the kidneys no longer work properly, receiving healthy kidney is the best way of treatment, called transplantation. After kidney transplantation (KT), the patient should receive several medicines to keep the new kidney healthy and protect it from rejection and failure. These medicines may help with immunity against the transplanted kidney or protect the kidney in general. One way the medicines may work is to decrease the effect of the hormone aldosterone, which helps control water and salt balance in the kidney by hanging on to sodium while releasing potassium from the body. By blocking aldosterone receptors, the body reduces protein leaking in the urine, controls blood pressure, minimizes kidney scarring, and protects against the hazardous effects of diabetes on the kidneys. Most evidence for these benefits comes from people who have not received a transplant, and transplant-specific studies are still small. In transplant recipients, these medicines may interact with anti-rejection therapy and can raise potassium. Care therefore requires careful patient selection, review of other medicines, and close monitoring of potassium, kidney function, and anti-rejection drug levels.
PMID:42669336 | DOI:10.1016/j.phrs.2026.108425