High Blood Pressure Drugs Could Harm Kidneys Over Time
Long-term use of RAS inhibitors may cause kidney damage, including scarring and loss of blood filtration function.
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A new study by researchers at the University of Virginia (UVA) School of Medicine has uncovered how prolonged use of renin-angiotensin system (RAS) inhibitors – commonly prescribed for high blood pressure – can harm the kidneys. While these drugs are effective at lowering blood pressure by relaxing blood vessels, their extended use can lead to severe kidney damage, including scarring and a loss of blood filtration function.
Renin-angiotensin system (RAS)
The RAS is a hormone system that helps regulate blood pressure and fluid balance. It involves enzymes like renin and angiotensin that control blood vessel constriction and water retention.RAS inhibitors work by blocking the enzyme renin, which regulates blood pressure. However, researchers observed that long-term inhibition overstimulates renin-producing cells, causing them to revert to an immature state. This triggers a cascade of changes:
- Growth of new nerves around renal arteries.
- Thickening of arterial walls due to excessive smooth muscle buildup.
- Scarring around blood vessels (arterioles).
- Infiltration of inflammatory cells.
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Subscribe for FREEThese changes result in a kidney that prioritizes producing renin over filtering impurities, contributing to vascular disease and further complicating blood pressure management.
Effects on kidney function
Using advanced 3D imaging, the researchers demonstrated that extended RAS inhibition leads to hyperinnervation, arteriolar hypertrophy, and immune cell infiltration in the kidneys. Together, these changes undermine the kidney's ability to clean the blood, turning it into what researchers describe as a “neuro-immune-endocrine organ.”
Arterioles
Arterioles are small blood vessels that branch from arteries and lead to capillaries. They play a crucial role in regulating blood flow and pressure.Hyperinnervation
Hyperinnervation refers to the excessive growth of nerve fibers in an organ or tissue. It can disrupt normal functions and contribute to disease.The study also emphasizes that the damage caused by these drugs is gradual and may go unnoticed until serious complications, such as reduced urination or swelling, emerge.
The global challenge of hypertension
Hypertension affects over 1.3 billion people globally, increasing the risk of heart disease, kidney failure, and stroke. RAS inhibitors remain a cornerstone of treatment due to their effectiveness, but the new findings suggest caution is needed for long-term use.
Patients using these medications are advised to monitor for signs of kidney damage and consult their healthcare providers regularly. Symptoms such as leg swelling, reduced urination, or seizures may indicate the need for a reassessment of treatment.
Future directions in treatment
The UVA team plans to further investigate the interactions between renin cells, smooth muscle cells, nerves, and inflammatory cells to identify strategies for mitigating kidney damage. By understanding the mechanisms behind these harmful changes, researchers aim to develop safer therapies for hypertension that avoid compromising kidney function.
Reference: Yamaguchi M, Almeida LFD, Yamaguchi H, et al. Transformation of the kidney into a pathological neuro-immune-endocrine organ. Circulat Res. 2024;135(10):1025-1027. doi: 10.1161/CIRCRESAHA.124.325305
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