NSAID Safety: GI Risks, Kidney Effects, and How to Monitor Them

Every year, millions of people reach for ibuprofen or naproxen to ease a headache, back pain, or arthritis flare-up. These drugs work fast. But what most users don’t realize is that NSAID safety isn’t just about whether the pain goes away-it’s about what’s happening inside your body while it does.

How NSAIDs Hurt Your Stomach-Even When You Feel Fine

NSAIDs block enzymes called COX-1 and COX-2. COX-2 causes inflammation and pain. COX-1 protects your stomach lining. When you take a regular NSAID like ibuprofen or naproxen, you’re not just turning off pain signals-you’re also disabling your stomach’s natural defense system.

This isn’t theoretical. About 1 in 5 people who take NSAIDs long-term develop a peptic ulcer. And here’s the scary part: half of those cases show no warning signs. No burning, no nausea, no warning. Just sudden bleeding-sometimes enough to land you in the ER.

It’s not just the stomach. NSAIDs also damage the small intestine. Studies using capsule endoscopy show that up to 70% of long-term users have tiny ulcers or erosions in their small bowel. These don’t cause obvious symptoms, but they can lead to chronic blood loss, iron deficiency, and fatigue you might never connect to your pain pills.

The risk isn’t equal across all NSAIDs. Naproxen carries a 4.2 times higher risk of upper GI bleeding than not taking any. Celecoxib, a COX-2 selective drug, cuts that risk nearly in half. But even celecoxib isn’t risk-free. And if you’re over 65, have a history of ulcers, or take blood thinners, your risk jumps even higher.

Your Kidneys Are Also at Risk

Your kidneys rely on prostaglandins to keep blood flowing through them. NSAIDs block those prostaglandins. That’s fine for a healthy kidney in a well-hydrated person. But if you’re dehydrated, older, or already have kidney issues, it’s dangerous.

Acute kidney injury from NSAIDs happens in 1% to 5% of users. It’s often reversible-if caught early. But for people with existing kidney disease, even a short course can push them into irreversible damage. The FDA now requires a boxed warning on all prescription NSAIDs for patients over 65, because the risk is real and often missed.

Chronic use can lead to more subtle damage: interstitial nephritis, fluid retention, high blood pressure, and even kidney papillary necrosis. These don’t show up on routine blood tests until it’s too late. That’s why monitoring isn’t optional-it’s essential.

Who’s Most at Risk?

Not everyone needs the same level of caution. But if you fit any of these categories, you’re in the danger zone:

• Age 65 or older
• History of peptic ulcer or GI bleeding
• Taking blood thinners like warfarin or aspirin
• Using corticosteroids (like prednisone)
• Having heart failure, liver disease, or chronic kidney disease
• Dehydrated or on diuretics

The American College of Gastroenterology has a simple scoring system: add up points for each risk factor. Four or more points? You’re high risk. That means you shouldn’t start NSAIDs without talking to your doctor about alternatives or protective measures.

Monitoring: What You Need to Check and When

If you’re taking NSAIDs for more than a few weeks, you need basic lab checks. Not because you feel bad-but because you might not feel anything until it’s too late.

Here’s what your doctor should track:

• Serum creatinine and eGFR: Check within 30 days of starting, then every 3-6 months if you’re on long-term therapy. A rise of 0.3 mg/dL or more in 48 hours could mean kidney injury.
• Complete blood count (CBC): Look for low hemoglobin or hematocrit. Iron deficiency anemia can be the only sign of slow, hidden bleeding.
• Fecal occult blood test: Recommended every 6 months for high-risk users. New point-of-care tests can detect even tiny amounts of blood in stool with 92% accuracy.
• Blood pressure: NSAIDs can raise it by 5-10 mmHg. Check it at every visit.

Many patients never get these tests. A 2023 Medicare analysis found only 52% of NSAID users had creatinine checked within 90 days of starting. That’s not just negligence-it’s a ticking time bomb.

What About PPIs? Are They the Answer?

Doctors often prescribe proton pump inhibitors (PPIs) like omeprazole alongside NSAIDs to protect the stomach. And yes-they work. They cut ulcer risk by 70-90%.

But here’s the catch: PPIs aren’t harmless. Long-term use with NSAIDs increases the risk of microscopic colitis by over six times. That means chronic, watery diarrhea you can’t explain. And PPIs don’t help your small intestine or kidneys at all.

Some patients feel better on PPIs and assume they’re protected. They’re not. You’re still at risk for silent bleeding, kidney damage, and new side effects from the PPI itself.

What Should You Do Instead?

The safest NSAID is the one you don’t take. Before reaching for another pill, ask yourself:

• Can I use acetaminophen instead? It doesn’t hurt your stomach or kidneys.
• Can I try physical therapy, heat, or topical creams for joint pain?
• Is there a non-drug option-like weight loss, braces, or stretching-that could reduce my need for pills?

If you must use NSAIDs:

• Use the lowest dose that works.
• Take it for the shortest time possible. Each extra week raises your complication risk by 3-5%.
• Choose celecoxib over naproxen or ibuprofen if you’re at high GI risk.
• Avoid combining NSAIDs with SSRIs (like sertraline)-that triples your bleeding risk.
• Stay hydrated. Don’t take NSAIDs on an empty stomach or when you’re dehydrated.

What’s New in 2025?

There’s hope on the horizon. Naproxcinod, a new NSAID that releases nitric oxide, showed 58% fewer stomach ulcers than naproxen in trials. It’s not yet widely available, but it’s a step toward safer pain relief.

Also, AI is being tested to spot early signs of intestinal damage during routine endoscopies. And new stool tests can now detect NSAID-related bleeding with high precision-making screening easier than ever.

But the biggest change? Awareness. More doctors are now using EHR alerts to flag high-risk patients. Pharmacies in the UK and US are starting pharmacist-led NSAID monitoring programs-and they’ve cut complications by 31%.

When to Stop and Call Your Doctor

Don’t wait for a crisis. Call your doctor if you notice:

• Black, tarry stools or blood in stool
• Unexplained fatigue, dizziness, or pale skin (signs of anemia)
• Swelling in ankles or sudden weight gain (possible kidney fluid retention)
• Reduced urine output or persistent nausea
• Any new pain in your stomach that doesn’t go away

These aren’t normal side effects. They’re red flags.

NSAIDs are powerful tools. But like any tool, they’re dangerous in the wrong hands. The goal isn’t to scare you off pain relief-it’s to help you use it wisely. Your stomach and kidneys can’t tell you they’re in trouble. Someone else has to speak for them.

What Comes Next?

If you’ve been taking NSAIDs for months or years, don’t panic. But do take action. Talk to your doctor about your risk level. Ask for a creatinine check and CBC if you haven’t had one in the last six months. Consider whether you really need the medication anymore-or if there’s a safer alternative.

NSAIDs saved lives and eased pain for decades. But we now know they’re not harmless. The next step in pain management isn’t just finding stronger drugs-it’s using the ones we have more wisely.