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Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Kidney

What are NSAIDs?

NSAIDs are a class of medications used to treat pain, fever and inflammatory conditions. They are among the most widely used mediations. More than 30 million people use NSAIDs every day.(Singh, 2000) They account for over 60% of the US over-the-counter analgesic market.


What are some of the commonly used NSAIDs?

Based on FDA approved classification, NSAIDs can be classified as:


Non-selective NSAIDs

·         Diclofenac

·         Ibuprofen

·         Indomethacin

·         Ketorolac

·         Naproxen

·         Sulindac


COX-2 Selective NSAIDs

·         Celecoxcib

·         Refecoxcib


How do NSAIDs work?

NSAIDs inhibit the enzymes cyclooxygenase (COX) which is needed to convert the arachidonic acid into thromboxanes, prostaglandins and prostacyclins. Relief in pain, reduction in inflammation results from lack of these molecules when NSAIDs inhibit the COX pathway.


What are the adverse effects resulting from NSAIDs use?

·         Renal adverse effects

·         Gastric adverse effects (peptic ulcer, hemorrhage, perforation)

·         Cardiovascular adverse effects (increased odds of having heart attacks)

·         Hepatic adverse effects (increased liver enzyme level)

·         Hematologic adverse effects (bleeding disorders)


What are the common renal (kidney related) consequences of using NSAIDs?


Sodium retention/swelling and high blood pressure

Use of both selective and nonselective NSAIDs may result in significant sodium retention, edema and hypertension. (Figures 13.2 and 13.8)


The Cyclooxygenase Pathway

Integrated role of PGE2 on the regulation of salt and water excretion from kidneys

Acute Kidney Injury (AKI)

Acute kidney injury (AKI) is a well-described complication of NSAIDs use. (Harris, 2016) NSAID-associated renal insufficiency occurs in patients who have underlying volume depletion, renal insufficiency, congestive heart failure, diabetes and advanced age. This has been seen with use of both COX-2-selective and nonselective NSAIDs (Ibuprofen, naproxen, ketorolac).

 

Interstitial Nephritis

Continuous NSAIDs use can lead to acute to subacute inflammatory kidney condition known as interstitial nephritis marked as reduction in filtration function of urine (reduction in GFR), sudden onset skin rash, hypertension and edema. This is generally a state of immune dysfunction triggered by drug exposure (NSAIDs in this case) Figure 35.1 . Acute interstitial nephritis tends to have a prompt and generally good response to steroids. Symptoms tend to abate rapidly following discontinuation of the NSAIDs.


acute tubulointerstitial nephritis

Nephrotic syndrome

Along the spectrum of immune mediated disturbance associated with NSAID use is nephrotic syndrome. This not so rare condition is marked by a constellation of features such as development of significant edema (anasarca), protein and fat leakage in urine, high blood cholesterol in blood, development of blood clots and more importantly decrease in kidney function. Figure 31.4. The mechanism of development of nephrotic syndrome following NSAID exposure remains yet to be fully elucidated.

electron micrograph of glomercular capillary wall

Papillary necrosis (Figure 196.4 Oxford)

-term use Longof NSAID has been associated with papillary necrosis and progressive renal structural and functional deterioration. Though incidence of papillary necrosis has decreased with an increasing awareness of avoidance of long term and especially heavy use of analgesics including NSAIDs.


papillary necrosis and progressive renal structural and functional deterioration

NSAIDs are highly effective pain killers and can be of much help in pain reduction but they should be used sparingly and judiciously. Please consult your doctor/PCP if you need guidance in using these medications on a more generous use.


For more information or inquiries, get in touch with a certified kidney doctor and specialist such as Dr. Prince Singh by emailing princesingh84@gmail.com or calling 507-316-3907

 

The information provided is for educational purposes and is not intended as a replacement for clinical advice. Always consult with your doctor for any drug related query.

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