Beta-blockers and CKD
Basics
This article attempts to highlight the importance of beta-blockers in the management of chronic renal failure. Chronic kidney disease (CKD) is associated with sympathetic overactivity. This occurs in order to maintain a constant eGFR. Beta-blockers are underused in CKD due to fears of adverse hemodynamic changes as well as the metabolic effects in patients with diabetes mellitus. However, a particular class of beta-blockers known as vasodilating B-blockers has been associated with neutral biochemical effects and they may be useful in the management of CKD.
Types of Beta-Blockers
Non-Selective Beta-Blockers
- Common agents: Propranolol
- Block: These agents block the Beta-1 and Beta-2 receptors.
- Problems: Decreases the eGFR and Renal Blood Flow (RBF) by lowering cardiac output (by blocking the Beta-1 receptors). This will cause a reflex response that stimulates the sympathetic nervous system and raises systemic and renal vascular resistance (by the activation of alpha-1 receptors). This agent also blocks the Beta-2 dependent vasodilation, leaving the alpha-1-mediated vasoconstriction unopposed. Therefore, one can assume that these agents should not be used in chronic kidney disease.
Selective Beta-Blockers
- Common agents: Metoprolol and Atenolol
- Block: These agents block the Beta-1 receptors. These agents may be used in patients with CKD with proven beneficial effects on the rate of decline in the patient’s renal function.
- Both these agents can increase renal vascular resistance (due to reflex activation of RAAS), however, they do not produce a significant reduction in the eGFR or the renal blood flow. Therefore, one can assume that the effects aren’t as bad as with non-selective beta-blockers.
- Atenolol has also been proven to prevent progression to macroalbuminuria when used in patients with microalbuminuria due to diabetic nephropathy.
- Metoprolol does not require renal dose adjustment, however, atenolol needs to be reduced by ½ to ¾ of its normal dose.
Vasodilating Beta-Blockers:
- Common agents: Labetalol and Carvedilol.
- Block: Labetalol and Carvedilol are non-selective beta-antagonists with alpha-1 inhibiting activity. Carvedilol also has antioxidant properties.
- The added blockage of alpha receptors results in decreased vascular resistance and hence they also preserve the renal blood flow and the eGFR (unlike the non-selective B-blockers).
- Carvedilol has also been shown to decrease the levels of microalbuminuria.
Conclusion
Chronic kidney disease is commonly associated with a state of sympathetic nervous system hyperactivity. CKD is also often found in patients with other comorbidities such as hypertension, diabetes, and heart failure. These patients may benefit from agents that have anti-adrenergic activity. It has been proven that some of these agents reduce the rate at which renal function deteriorates. However, it is known that Beta-blockers are still underutilized in the management of CKD. This is due to the fear of negatively affecting the renal function and glycemic control of the patient. This may be due to the fact that atenolol was used in many of the studies done involving Beta-blockers and CKD. As noted already, atenolol (although good) is not the best beta-blocker for these patients and one should rather consider a vasodilating beta-blocker instead. However, further studies are needed.
2. Kalaitzidis, R. and Bakris, G. (2008) “Should nephrologists use beta-blockers? A perspective,” Nephrology Dialysis Transplantation, 24(3), pp. 701–702. Available at: https://doi.org/10.1093/ndt/gfn695.
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