Optimal Diuretic Selection for Hypertension Treatment by Patient Profile

Jump To Section

• Chronic Kidney Disease and Hypertension
• Primary Aldosteronism Treatment
• Resistant Hypertension Management
• Potassium's Role in Blood Pressure
• Dual-Action Diuretic Mechanisms
• Full Transcript

Chronic Kidney Disease and Hypertension

Dr. David Ellison, MD, emphasizes that hypertension in chronic kidney disease patients is often volume-driven. These patients typically have excess extracellular fluid volume due to salt retention. Diuretics are strongly recommended for blood pressure control in this population.

Traditionally, loop diuretics were preferred for advanced chronic kidney disease. Medical teaching held that thiazides lost potency as kidney function declined below a glomerular filtration rate of 50. Dr. Ellison, MD, explains that new research from Dr. Rajiv Agarwal has changed this view. A study published in the New England Journal of Medicine showed chlorthalidone's efficacy even in stage four chronic kidney disease.

Primary Aldosteronism Treatment

Dr. David Ellison, MD, identifies primary aldosteronism as another key indication for specific diuretics. This condition involves either aldosterone-producing tumors or adrenal gland hyperplasia. Blocking aldosterone's actions is crucial for effective blood pressure management in these patients.

Spironolactone serves as the primary treatment for aldosterone-related hypertension. Dr. David Ellison, MD, notes that eplerenone offers an alternative with fewer side effects. However, eplerenone may be slightly less effective than spironolactone for controlling blood pressure in these conditions.

Resistant Hypertension Management

Dr. David Ellison, MD, discusses the PATHWAY trial published in The Lancet that revolutionized resistant hypertension treatment. This randomized trial examined various drug classes for patients with difficult-to-control blood pressure. Spironolactone emerged as the most effective add-on medication.

The research showed that elevated aldosterone levels are not necessary for spironolactone response. Dr. David Ellison, MD, recommends adding spironolactone to any resistant hypertension regimen. Amiloride provides another effective option for patients who cannot tolerate spironolactone.

Potassium's Role in Blood Pressure

Dr. David Ellison, MD, explains the critical relationship between serum potassium levels and blood pressure regulation. Potassium serves as the most important regulator of the thiazide-sensitive sodium chloride cotransporter. Low potassium levels activate this transporter, causing increased salt retention.

This mechanism explains why hypokalemia can counteract thiazide diuretic effects. Dr. David Ellison, MD, emphasizes preventing potassium depletion during thiazide therapy. Maintaining adequate potassium levels ensures optimal response to thiazide diuretics for hypertension treatment.

Dual-Action Diuretic Mechanisms

Dr. Ellison describes how spironolactone and amiloride provide dual-action benefits for hypertension. These medications block sodium channels in the kidney's collecting duct. They simultaneously raise serum potassium levels, which inhibits the thiazide-sensitive transporter.

This dual mechanism makes these drugs particularly effective for blood pressure control. Dr. David Ellison, MD, recommends adding these agents when thiazides cause hypokalemia. The approach addresses both potassium balance and enhanced blood pressure reduction through multiple pathways.

Full Transcript

Dr. Anton Titov, MD: Diuretics to treat hypertension may fit best certain patient profiles. What are those patient profiles?

Dr. David Ellison, MD: There are certain types of hypertension for which specific drugs are recommended. For the average run-of-the-mill hypertension, as we just discussed, any of the classes of drugs, any of the three classes we mentioned, is probably fine.

In patients who have chronic kidney disease, especially advanced chronic kidney disease, there is no question that those patients have blood pressure elevations that are driven largely by excess extracellular fluid volume, which means excess salt. So in patients with chronic kidney disease, we especially emphasize the use of diuretic drugs. If those patients become resistant to their hypertensive regimen, we absolutely will escalate the use of diuretics.

Traditionally, in chronic kidney disease, we turn to loop diuretics to treat hypertension rather than thiazide diuretics. What's taught to medical students for many years is that thiazide diuretics lose their potency as one’s kidney function begins to deteriorate. We used to teach that you needed to switch from a thiazide diuretic to a loop diuretic as the glomerular filtration rate got below, say, 50.

I think that view has changed recently because of a very nice study done by Rajiv Agarwal at Indiana University and published recently in the New England Journal of Medicine. He took patients with advanced chronic kidney disease, stage four chronic kidney disease, and instead of using loop diuretics, he added a thiazide diuretic, chlorthalidone, which is a very good thiazide diuretic.

He also pushed the doses a little bit higher than we typically use for treating run-of-the-mill hypertension. But he was able to show strong efficacy of chlorthalidone even in patients with advanced chronic kidney disease to reduce their blood pressure.

I guess I'd summarize that aspect by saying this. In patients with chronic kidney disease, usually their blood pressure is volume-driven. Usually, it's salt-driven.

Dr. David Ellison, MD: We strongly emphasize the use of diuretics. While loop diuretics are effective, we now think that thiazide diuretics, and especially chlorthalidone, should be a good alternative and should be considered in these patients.

The second type of hypertensive patient where a specific diuretic is indicated is in patients who have primary aldosterone problems, either from an aldosterone tumor or, more importantly, from hyperplasia of the adrenal gland, which is the more common type of high aldosterone problem. In those patients, it's really important to block the specific actions of aldosterone.

Most commonly, we would do that with spironolactone, which blocks the actions of aldosterone. You can also use eplerenone, which has fewer side effects than spironolactone. But eplerenone is probably a little less effective at the end of the day.

So those are two specific situations. The third situation, which is really important to emphasize, is that we now recognize that in patients who have resistant hypertension, whether or not they have hyperaldosteronism, they still respond very well to the use of spironolactone or alternatively to amiloride, the direct sodium channel blocking drugs that work in the collecting duct.

Dr. David Ellison, MD: Patients with resistant hypertension—this is another beautiful randomized trial called the PATHWAY trial published a couple of years ago in the Lancet—in which they examined several different classes of drugs in patients with resistant hypertension. They found that spironolactone or amiloride, parenthetically, but spironolactone specifically, was the most effective add-on drug for patients with resistant hypertension.

Again, if you look at the data, it's very clear that you don't have to have elevated aldosterone levels in order to respond to spironolactone with a positive reduction in blood pressure.

Dr. David Ellison, MD: Even though we recommend screening everybody for primary aldosteronism, and if you have it, definitely treat with spironolactone, even if you don't have it, if your blood pressure is difficult to treat, now we recommend adding spironolactone to your regimen. It's quite effective.

One of the other things we've recognized recently, in terms of this interaction between sodium, potassium, and aldosterone and blood pressure that we didn't recognize before, is that serum potassium level is the most important regulator of the thiazide-sensitive sodium chloride cotransporter. The transporter that's blocked by thiazide diuretics is actually regulated by the serum potassium level.

It turns out that the transporter is turned on when the serum potassium level goes down.

Dr. David Ellison, MD: We know that this is important for the body's homeostatic regulation of the ability to get rid of potassium. But this actually can contribute to the hypertension that develops when people don't eat enough potassium because it activates their thiazide-sensitive transporter, and they retain more salt.

That also explains why, if you give a thiazide diuretic and the patient becomes hypovolemic and has a low serum potassium level, that then turns on the thiazide-sensitive transporter and essentially counteracts the effects of thiazides. So the side effect actually is blocked when one develops hypokalemia.

That's why we think it's very important to prevent hypokalemia when you're treating a patient with a thiazide diuretic. We also now know that one of the reasons that amiloride and spironolactone are effective at lowering blood pressure is not just because they block the actions of aldosterone on the distal nephron and block the sodium channel in the distal nephron.

Because they raise blood potassium, they also inhibit the thiazide-sensitive cotransporter. So they really block two different transporters in the kidney. They block the sodium channel in the collecting duct, and they block the thiazide-sensitive transporter in the distal convoluted tubule.

You really get to kill two birds with one stone, if you will. So that's one of the reasons these drugs are really so effective. It is because of that dual action.

That's why we often add them on top. If somebody develops hypokalemia when they're on a thiazide diuretic, you can just add a little bit of spironolactone or amiloride and raise the blood potassium. That's really an effective approach to treating hypertension.