“With cardiovascular disease being the leading cause of death in adults worldwide, prescribing safe and effective anti-hypertensive therapies is of great concern. However, a common combination of renin-angiotensin system (RAS) inhibitors, such as angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), with diuretics and easily accessible over the counter non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney damage.”

Beware Kidney Injury From the Triple Whammy!

Some common medications are linked to kidney injury when taken together (“triple whammy”): NSAIDs, diuretics and ARB or ACEi BP medications.

Beware Kidney Injury From the Triple Whammy!

From the Website of Graedon:

May 05, 2022

Tens of millions of Americans are at risk for kidney injury. That’s because they are taking a combination of drugs that researchers refer to as the “triple whammy” (Mathematical Biosciences, May, 2022). The medications in question involve diuretics, ACE inhibitor or ARB blood pressure drugs and NSAID pain relievers such as ibuprofen. This combination is surprisingly common. According to the authors of the research paper: “This triple therapy, known as “triple whammy”, was associated with a 31% increased risk for acute kidney injury (AKI), compared to patients treated with diuretic and ACEI/ARB only.”

What Drugs Are Involved?

Diuretics:

Let’s name names! Diuretics are prescribed in huge quantities, either alone or in combination with blood pressure meds. The most common diuretic is hydrochlorothiazide (EsidrixHydrodiuril). Over 9 million people take it daily all by itself. There are other diuretics, though. They include furosemide (Lasix), chlorthalidone (Hygroton), bumetanide (Bumex), indapamide (Lozol) and chlorothiazide (Diuril).

Hydrochlorothiazide (HCTZ) is often combined with other BP drugs such as lisinopril or losartan. When HCTZ is combined with the potassium sparing diuretic called triamterene, the combination is called Dyzazide or Maxzide.

BP Drugs Include:

The top selling ACE inhibitor is lisinopril. At last count, 20 million people take this drug daily.

Other ACE Inhibitors: NY remark

  • Benazepril (Lotensin)
  • Captopril (Capoten)
  • Enalapril (Vasotec)
  • Fosinopril (Monopril)
  • Lisinopril (Prinivil, Zestril)
  • Moexipril (Univasc)
  • Perindopril (Aceon)
  • Quinapril (Accupril)
  • Ramipril (Altace) my remark probably the most often used Iisrael

ARBs (Angiotensin Receptor Blockers) Are Also Common:

  • Atacand (candesartan)
  • Avapro (irbesartan)
  • Benicar (olmesartan)
  • Cozaar (losartan) my remark: losartan and valsartan are probably the most often used in Israel
  • Diovan (valsartan)
  • Edarbi  (azilsartan)
  • Micardis (telmisartan)
  • Teveten (eprosartan)

Losartan is the most popular. We calculate that around 10 million people take this drug daily.

NSAIDs Are OTC or Rx:

  • Ibuprofen (Advil, Motrin) my remark: widely overused in Israel, available over the counter!!
  • Naproxen (Aleve)
  • Celecoxib (Celebrex)
  • Diclofenac (Cataflam, Voltaren)
  • Indomethacin (Indocin)
  • Meloxicam (Mobic)

Tens of million of people take an NSAID every day to control pail.

Kidney Injury and the Triple Whammy:

With so many people taking each of these different kinds of medications it is not surprising that a lot of people could end up swallowing the triple whammy. Imagine a person with hypertension taking HCTZ and lisinopril develops a headache or a muscle strain. The chances are good that individual might reach for ibuprofen to ease the discomfort. That could lead to kidney injury, according to the recent report (Mathematical Biosciences, May, 2022).

Here is how the authors introduce their research:

“With cardiovascular disease being the leading cause of death in adults worldwide, prescribing safe and effective anti-hypertensive therapies is of great concern. However, a common combination of renin-angiotensin system (RAS) inhibitors, such as angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), with diuretics and easily accessible over the counter non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney damage.”

How Does the Triple Whammy Trigger Kidney Injury?

We won’t go into the complex physiology of triple whammy treatment. The bottom line seems to be that this combination of drugs can lead to “dangerously low GFR [glomerular filtration rate]”. This is a test of how well blood is passing through the kidneys.

The authors are quick to note that not everyone develops kidney injury from the triple whammy. What makes some people more vulnerable? Some people have a harder time regulating blood flow through the kidney than other folks. Other people who are at risk include those who may become dehydrated.

What Can People Do To Avoid Kidney Injury?

If you are taking an ACE inhibitor or an ARB along with a diuretic, please drink water. The authors of this research mention “low water intake” as a risk factor when people are on triple whammy drug therapy.

Another consideration might be to avoid NSAIDs while taking diuretics and BP meds such as ACE inhibitors or ARBs. Ask your doctor is acetaminophen might be safer for pain management than an NSAID.

What About Exercise for the Kidneys?

As people get older their kidney function tends to decline. Researchers wondered whether a structured, moderate-intensity exercise intervention might be beneficial (JAMA Internal Medicine, May 2, 2022). They recruited nearly 1200 sedentary senior citizens between 70 and 89 years of age. People were randomized to either a 2-year exercise program or health education.

The volunteers wore accelerometers to monitor their physical activity. The people who participated in the exercise intervention had less kidney function decline compared to the people who received health education. The authors suggest that doctors:

“…should consider prescribing physical activity and moderate-intensity exercise for older adults to slow the rate of decline of kidney function.”

Final Words:

Most people take their kidney function for granted until it starts to go south. But kidneys are essential for good health. Avoiding kidney injury should be a key health strategy! One way to do that is to avoid the triple whammy drug combination. Another way is to avoid other drugs that might pose problems to kidney health. Another category of drugs that could pose a problem are proton pump inhibitors for heartburn. If you want to read more about this risk, here is a link:

More Bad News About PPIs and Kidney Damage

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