Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) prescribed to manage pain and inflammation associated with conditions such as osteoarthritis and rheumatoid arthritis. Like other medications in its class, diclofenac works by interrupting the body’s inflammatory signaling pathways. However, the same mechanism that provides pain relief also introduces a potential risk to kidney function. Understanding how this medication interacts with the kidneys is important for anyone using it, especially those with pre-existing health conditions. This article explores the ways diclofenac can impact renal health, the types of injury that may occur, and the signs and risk factors associated with kidney impairment.
How Diclofenac Works and Its Connection to Kidney Function
Diclofenac exerts its therapeutic effects by inhibiting cyclooxygenase (COX) enzymes, specifically both COX-1 and COX-2. These enzymes convert a fatty acid into signaling molecules called prostaglandins. By blocking COX, diclofenac suppresses the production of prostaglandins, which drive pain, inflammation, and fever.
This action becomes problematic in the kidney because prostaglandins play a protective role in maintaining renal blood flow. The kidneys produce prostaglandins, such as prostacyclin (PGI2) and prostaglandin E2 (PGE2), to help regulate their own circulation. These signaling molecules dilate the afferent arteriole, the small blood vessel that supplies blood to the filtering unit of the kidney, known as the glomerulus.
When the body is stressed, such as during dehydration or low blood pressure, the kidney relies heavily on this prostaglandin-mediated dilation to ensure adequate blood supply for filtration. Diclofenac’s inhibition of COX enzymes prevents this protective synthesis, causing the afferent arteriole to constrict instead. This constriction reduces the amount of blood flowing into the glomerulus, leading to a drop in the glomerular filtration rate (GFR).
This hemodynamic change—a reduction in blood flow—is the fundamental basis for the potential kidney harm caused by diclofenac and other NSAIDs.
Types of Renal Injury Associated with Diclofenac Use
The most frequently observed form of kidney damage linked to diclofenac use is acute kidney injury (AKI). AKI is characterized by a rapid decline in the kidney’s filtering ability over hours or days. This injury is primarily hemodynamic, resulting directly from the reduced blood flow to the glomerulus caused by prostaglandin suppression.
This acute renal dysfunction is often reversible, and kidney function can recover once the medication is stopped. Reduced blood flow can also lead to acute tubular necrosis, where the cells lining the kidney tubules are damaged and die.
A less common, but more severe, type of injury is acute interstitial nephritis (AIN), which is an immune-mediated reaction. AIN involves inflammation of the tissue surrounding the kidney tubules, often considered a hypersensitivity response to the drug. This injury can lead to significant renal damage and may require temporary hemodialysis.
Prolonged use of high doses of diclofenac carries the risk of chronic kidney disease (CKD) and renal papillary necrosis. Papillary necrosis involves the structural death of the renal papillae, the tips of the kidney pyramids where urine is collected. This permanent structural damage is a progressive consequence of long-term NSAID use, potentially leading to irreversible kidney impairment.
Risk Factors and Signs of Kidney Impairment
Certain patient characteristics and medical conditions significantly increase the risk of diclofenac-induced kidney impairment. Individuals with pre-existing kidney disease are the most vulnerable, as their kidneys have less functional reserve to cope with the drug’s effect on blood flow. Advanced age is also a major risk factor because renal function naturally declines.
Dehydration or hypovolemia, such as that caused by illness or low blood pressure, stresses the kidneys and makes them more susceptible to the drug’s vasoconstrictive effects. The risk is compounded when diclofenac is taken alongside other medications that affect the kidneys or blood pressure, such as diuretics or ACE inhibitors and ARBs. This combination, sometimes referred to as the “triple whammy,” severely limits the kidney’s ability to regulate its own function.
Patients should be aware of warning signs that may indicate reduced kidney function or fluid retention.
Signs of Impairment
Common physical signs include swelling, particularly in the legs, ankles, or feet. Other symptoms involve a noticeable decrease in the amount of urine produced, or painful and difficult urination. Systemic symptoms such as unusual fatigue, nausea, vomiting, and feeling short of breath can also point toward kidney issues.
To minimize risk, patients should use diclofenac at the lowest effective dose for the shortest possible duration. Maintaining adequate hydration is important, and anyone with existing risk factors should consult a healthcare professional for routine monitoring of renal function while taking the drug.