Question: I’m at a conference and the speaker (who is a nephrologist) says ACE inhibitors (used to protect the kidneys and decrease high blood pressure) may worsen kidney function (they can increase the creatinine and cause the GFR to go down). Two questions: Wow do they cause the creatinine to go up and the GFR to go down? And why do we use ACE inhibitors if they worsen kidney function?
Dr. Aaronson: Angiotensin Converting Enzyme (ACE) inhibitors lower blood pressure. ACE inhibitors prevent the formation of a hormone called angiotensin II, which normally causes blood vessels to constrict, or to become narrower. ACE inhibitors allow the arterial blood vessels to relax (open up), and the result is lowered blood pressure.
Examples of ACE inhibitors include:
- Enalapril (Vasotec)
- Ramipril (Altace)
- Quinapril ( Accupril)
- Perindopril (Aceon)
- Lisinopril (Prinivil/Zestril)
- Benazepril (Lotensin)
In addition to blood pressure lowering, ACE inhibitors have an added, beneficial effect on the kidneys. ACE inhibitors unload the kidney filters (the glomeruli) so that the kidney filters do not have to work as hard. ACE inhibitors dilate the efferent arterioles, or the vessels that travel away from the kidney. The kidney is the only organ system in the body where a vein is replaced by an artery.
Every other organ system in the body: artery -> capillary -> vein
The kidney filtering system: afferent artery -> capillary filter (glomerulus) -> efferent artery
Because of this switch, the kidneys have the ability to both constrict and dilate the efferent arteriole which allows for varying pressure on the filters of the kidneys and protection from dehydration and fluid overload.
So although the kidney function may worsen, the total time to dialysis is prolonged. That’s why we tolerate up to a 30 per cent increase in the creatinine as long as the patient does not suffer from high potassium (hyperkalemia) and acute kidney injury.
Additional side effects of ACE inhibitors include dry, hacking cough, low blood pressure, and a rash. For those people unable to tolerate ACE inhibitors, there are other options such as angiotensin receptor blockers which may be better tolerated in some individuals. Note that losartan is the only ARB that is generic. Be careful “asking your doctor for it” because losartan is still quite expensive, a three month supply of losartan costs $86.65 per month at drugstore.com while a three month supply of benazepril 40 mg daily is only $4.33 per month at the CHI Health Pharmacy.
In conclusion, realize there is a difference between markers of risk (surrogate markers) and clinical outcomes. Creatinine is a marker of risk. We use it to follow a person’s kidney function. However, the clinical outcome we want to prevent is the initiation of kidney dialysis. Therefore, if the creatinine increases “a little bit,” but the length of time to kidney dialysis is prolonged, the patient wins. In addition, the system wins and we help prevent the healthcare bubble from bursting. By using ACE inhibitors, we can effectively increase the amount of time until a patient with chronic kidney disease needs kidney dialysis.