Why do ace inhibitors decrease gfr
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Why ACE Inhibitors Decrease GFR
Introduction to ACE Inhibitors and GFR
Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for managing hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This inhibition leads to vasodilation, reduced blood pressure, and decreased workload on the heart. However, a notable side effect of ACE inhibitors is a reduction in glomerular filtration rate (GFR), which is a measure of kidney function.
Mechanism of Action: ACE Inhibitors and Renal Hemodynamics
Reduction in Angiotensin II Levels
Angiotensin II plays a crucial role in maintaining glomerular filtration pressure by constricting the efferent arterioles of the glomeruli. By inhibiting the formation of angiotensin II, ACE inhibitors cause dilation of these arterioles, leading to a decrease in glomerular capillary pressure and, consequently, a reduction in GFR .
Role of Bradykinin
ACE inhibitors also prevent the breakdown of bradykinin, a peptide that promotes vasodilation. Increased levels of bradykinin further contribute to the dilation of efferent arterioles, compounding the reduction in glomerular pressure and GFR.
Clinical Observations and Studies
Acute Effects in Diabetic Hyperfiltration
In diabetic patients with hyperfiltration, ACE inhibitors have been shown to significantly decrease GFR. This effect is primarily due to the reduction in angiotensin II levels, which leads to decreased glomerular pressure. Studies have demonstrated that while ACE inhibitors like ramiprilat reduce GFR in diabetic rats, this effect is not observed in non-diabetic controls, highlighting the specific impact on altered renal hemodynamics in diabetes.
Long-term Benefits Despite Initial GFR Reduction
Despite the initial reduction in GFR, long-term use of ACE inhibitors has been associated with renoprotective effects. For instance, in patients with chronic nephropathies, ACE inhibitors like ramipril have been shown to slow the progression of renal disease and reduce the incidence of end-stage renal disease (ESRD) . This paradoxical benefit is attributed to the reduction in proteinuria and stabilization of renal function over time.
Impact on Patients with Heart Failure
In patients with congestive heart failure (CHF), ACE inhibitors can cause an initial decline in GFR. However, this decline does not necessarily correlate with adverse outcomes. Studies have indicated that the early worsening of renal function (WRF) after initiating ACE inhibitors does not adversely affect long-term survival and may represent a benign event.
Conclusion
ACE inhibitors decrease GFR primarily by reducing angiotensin II levels, leading to the dilation of efferent arterioles and a subsequent drop in glomerular pressure. While this reduction in GFR can be concerning initially, the long-term benefits of ACE inhibitors in preserving renal function and preventing the progression of kidney disease are well-documented. Understanding the dual impact of ACE inhibitors on renal hemodynamics and their protective effects is crucial for optimizing their use in clinical practice.
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