NSAIDs Do Not Cause Kidney Stones, But May Cause Acute Kidney Injury
NSAIDs do not contribute to the formation of kidney stones. In fact, NSAIDs (particularly diclofenac, ibuprofen, and metamizole) are the first-line treatment for renal colic caused by kidney stones 1.
The Evidence on NSAIDs and Kidney Stones
The provided guidelines extensively discuss NSAID-related renal toxicity, but none mention kidney stone formation as a complication 2. The renal complications associated with NSAIDs are:
- Volume-dependent acute renal failure (reduced glomerular filtration)
- Interstitial nephritis
- Nephrotic syndrome
These occur because NSAIDs inhibit prostaglandin-mediated renal vasodilation, particularly in patients with pre-existing renal disease, heart failure, or cirrhosis 2.
Recent Mendelian Randomization Studies Show Conflicting Results
Two very recent Mendelian randomization studies from 2025 suggest a potential association between NSAIDs and kidney stones 3, 4, but these findings:
- Are based on genetic proxies, not actual NSAID use
- Have not been validated in clinical trials
- Contradict decades of clinical experience where NSAIDs are standard therapy for kidney stone pain
- Show only one specific genetic pathway (NEU1 expression) potentially linked to stones 4
The clinical reality is that NSAIDs are routinely prescribed to kidney stone patients without increasing stone recurrence risk. The 2025 European Association of Urology guidelines explicitly recommend NSAIDs as first-line treatment for renal colic 1, and the 2014 AUA Medical Management of Kidney Stones guideline makes no mention of NSAIDs causing stones 5.
What NSAIDs Actually Do to the Kidneys
The real concern with NSAIDs is acute kidney injury, not stone formation. Approximately 2% of patients taking NSAIDs will discontinue them due to renal complications 2. Risk factors include:
- Age >60 years
- Pre-existing renal disease
- Compromised fluid status
- Concomitant nephrotoxic drugs (ACE inhibitors, ARBs, cyclosporine, cisplatin)
- Heart failure or cirrhosis
Clinical Recommendations
Use NSAIDs cautiously in high-risk patients, but kidney stone formation is not a reason to avoid them 6. Monitor:
- Baseline and periodic creatinine/BUN
- Blood pressure (NSAIDs can worsen hypertension)
- Discontinue if creatinine doubles or hypertension worsens 6
For patients at high risk of renal complications, consider monitoring creatinine weekly for three weeks after NSAID initiation 2, though evidence that this monitoring improves outcomes is lacking.
Bottom line: NSAIDs treat kidney stone pain effectively and do not cause stones to form. The concern with NSAIDs and kidneys is acute injury from reduced renal perfusion, not nephrolithiasis.