Prevalence of NSAID-Induced Kidney Injury
Approximately 1-2% of patients taking NSAIDs will develop clinically detectable renal complications requiring drug discontinuation, though subclinical kidney injury occurs much more frequently. 1, 2
Overall Population Prevalence
Clinically detectable renal function abnormalities occur in approximately 1% of all NSAID-exposed patients, excluding mild fluid retention which affects virtually all users to some degree. 2
Approximately 2% of patients taking NSAIDs will discontinue them specifically due to renal complications. 1
Fluid retention occurs to some degree in virtually all NSAID users, but clinically detectable edema manifests in less than 5% of patients. 2
The pooled odds ratio for acute kidney injury with current NSAID exposure in the general population is 1.73 (95% CI 1.44-2.07), indicating a 73% increased risk compared to non-users. 3
High-Risk Population Prevalence
In older adults, the odds ratio for NSAID-induced AKI increases substantially to 2.51 (95% CI 1.52-2.68), representing a 151% increased risk. 3
In patients with pre-existing chronic kidney disease, the pooled odds ratio for AKI is 1.63 (95% CI 1.22-2.19), with individual studies showing ranges from 1.12 to 5.25. 3
Among hospitalized patients with acute kidney injury from NSAIDs, the mean serum creatinine peaked at 4.09 ± 4.24 mg/dL, with two patients requiring dialysis in one case series of 15 patients. 4
Subclinical Kidney Injury Prevalence
Subclinical kidney injury, detected by sensitive biomarkers (NGAL, KIM-1), occurs at much higher rates than clinically apparent injury, with biomarker levels rising 2-3 fold in regular NSAID users compared to controls despite normal serum creatinine. 5
Biomarkers of kidney injury begin rising as early as 7 days after starting regular NSAID therapy, indicating that subclinical damage occurs far more frequently than the 1-2% rate of clinically detected injury. 5
Types of Renal Complications and Their Relative Frequencies
Fluid retention and sodium retention are the most common complications, occurring to some degree in virtually all exposed individuals. 2
Acute deterioration of renal function (hemodynamic renal failure) is the next most common serious complication, occurring primarily in high-risk patients with compromised renal perfusion. 2
Hyperkalemia and other electrolyte complications occur infrequently, manifesting only in specific at-risk patients. 2
Nephrotic syndrome with acute interstitial nephritis is rare, occurring unpredictably and primarily with propionic acid derivatives. 2, 6
Papillary necrosis is very rare but represents the only permanent complication of NSAID use. 2
Critical Context for Clinical Practice
The absolute number of at-risk patients is substantial given widespread NSAID use, both prescription and over-the-counter, making this an under-recognized public health problem. 2, 4
The duration from onset to normalization of serum creatinine averages 37 ± 42 days, indicating that most patients with NSAID-induced AKI have abnormal renal function for a prolonged period even after drug discontinuation. 4
All cases of NSAID-induced acute kidney injury in one case series eventually recovered with normalization of serum creatinine, though recovery time was prolonged. 4
Risk Amplification with Specific Conditions
NSAIDs should be avoided entirely in patients with pre-existing renal disease, congestive heart failure, or cirrhosis due to extremely high risk of acute renal failure. 7
Risk increases substantially when NSAIDs are combined with ACE inhibitors, ARBs, or diuretics, creating compounded nephrotoxicity. 1
The combination of triamterene and indomethacin is especially nephrotoxic and should be avoided. 6