From the Guidelines
NSAIDs can cause significant renal impairment by inhibiting the synthesis of renal prostaglandins, which mediate vasodilation in the kidneys and directly inhibit sodium resorption in the thick ascending loop of Henle and collecting tubule, leading to sodium and water retention and blunting the effects of diuretics 1.
Key Effects of NSAIDs on Renal Function
- Sodium and water retention: NSAIDs can cause sodium and water retention, which can lead to increased blood pressure and decreased renal function 1.
- Blunting of diuretic effects: NSAIDs can blunt the effects of diuretics, making them less effective in treating conditions such as heart failure and ascites 1.
- Acute renal failure: The use of NSAIDs, such as indomethacin, ibuprofen, aspirin, and sulindac, can lead to acute renal failure, hyponatremia, and diuretic resistance in patients with cirrhosis and ascites 2.
- Reduced glomerular filtration rate: NSAIDs can reduce renal perfusion secondary to inhibition of renal prostaglandin synthesis, leading to a reduced glomerular filtration rate 2.
Patient Populations at Risk
- Patients with heart failure: NSAIDs can increase morbidity and mortality in patients with heart failure 1.
- Patients with cirrhosis and ascites: NSAIDs should not be used in patients with cirrhosis and ascites due to the high risk of acute renal failure, hyponatremia, and diuretic resistance 2.
- Patients with chronic kidney disease: People with diabetes are at higher risk of acute kidney injury (AKI) than those without diabetes, and the use of NSAIDs can further increase this risk 3.
Recommendations for NSAID Use
- Use the lowest effective dose for the shortest duration: Clinicians should prescribe the lowest effective dose of NSAIDs for the shortest duration to minimize the risk of renal impairment and other complications 4.
- Monitor renal function: Patients taking NSAIDs should be monitored for signs of renal impairment, such as increased serum creatinine and decreased glomerular filtration rate 2, 3.
From the Research
Effects of NSAIDs on Renal Function
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can affect renal functions dependent upon prostaglandin synthesis, as they inhibit cyclooxygenase 5.
- In normal individuals, renal function is relatively independent of the prostaglandin system, and NSAIDs usually do not produce renal dysfunction 5.
- However, in certain circumstances, such as salt retention or renal vascular damage, NSAIDs can reduce renal blood flow and glomerular filtration rate, leading to acute renal failure that is reversible upon discontinuation of the drug 5.
Renal Complications Associated with NSAIDs
- NSAIDs can cause various renal complications, including: + Reduction of sodium excretion and blunting of the diuretic effect of loop diuretics, leading to edema 5. + Inhibition of prostaglandin-dependent renin secretion, occasionally resulting in hyperkalemia 5. + Enhancement of the antidiuretic effects of vasopressin 5. + Reduction of the antihypertensive efficacy of several drugs 5.
- Acute kidney injury (AKI) is a significant risk associated with NSAID use, particularly in patients with underlying renal disease or those taking other nephrotoxic medications 6, 7.
- Chronic consumption of NSAIDs can lead to chronic kidney disease (CKD) and tubulointerstitial nephritis (TIN) 7.
Mechanism of NSAID-Induced Renal Damage
- The mechanism of NSAID-induced renal damage is associated with the inhibition of prostaglandin synthesis, which affects renal blood flow and glomerular filtration rate 8, 9.
- Both COX-1 and COX-2 isoforms play opposing roles in renal function, with COX-1 inhibition increasing natriuresis and reducing blood pressure, and COX-2 inhibition increasing blood pressure and promoting sodium retention 7.
- TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density, leading to nephrotic proteinuria and impairment of renal function 7.