Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population

doi:10.1053/j.ajkd.2004.12.005

American Journal of Kidney Diseases

Volume 45, Issue 3, March 2005, Pages 531-539

https://doi.org/10.1053/j.ajkd.2004.12.005 Get rights and content

Background: Most epidemiological studies evaluating the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute renal failure (ARF) found an increased risk for developing ARF while taking NSAIDs. Despite these studies, little is known about the effect of dose and duration of therapy, risk of individual NSAIDs, comorbidity, or concomitant use of other nephrotoxic drugs. Methods: This is a nested case-control study using the General Practice Research Database from the United Kingdom. Participants were 386,916 patients aged 50 to 84 years on January 1, 1997, and free of known cancer, renal disorder, cirrhosis, or systemic connective tissue disease. After validation of cases identified from this cohort, 103 patients were confirmed as idiopathic cases of ARF and compared with 5,000 controls frequency matched by age and sex. Results: Current users of NSAIDs had a relative risk (RR) for ARF of 3.2 (95% confidence interval [CI], 1.8 to 5.8), and the risk declined after treatment was discontinued. Increased risk was present with both short- and long-term therapy and was slightly greater among users of high doses. History of heart failure (HF), hypertension, diabetes, and hospitalizations and consultant visits in the previous year were all associated with a greater risk for ARF. There was a suggestion of a modification of the effect of NSAIDs in patients with hypertension and those with HF. Use of selected cardiovascular drugs was associated with a 5-fold increase in risk for ARF. Diuretics presented the greatest risk. Risk increased with concomitant use of NSAIDs and diuretics (RR, 11.6; 95% CI, 4.2 to 32.2) and NSAIDs and calcium channel blockers (RR, 7.8; 95% CI, 3.0 to 20.5). Conclusion: NSAID users had a 3-fold greater risk for developing a first-ever diagnosis of clinical ARF compared with non–NSAID users in the general population. NSAIDs should be used with special caution in patients with hypertension and/or HF.

Section snippets

Data source

The GPRD contains computerized medical information entered systematically by general practitioners (GPs) and sent anonymously to the Medicines and Healthcare Products Regulatory Agency,¹⁶ which organizes this information to be used for research projects. The information recorded includes demographic data, medical diagnoses from GP visits, specialist referrals and hospitalizations, results of laboratory tests, a free-text section, and all prescriptions issued. Prescriptions are generated

Results

The incidence of nonfatal ARF in our study was 1.1 cases/10,000 person-years. Of 103 newly diagnosed cases of ARF, 38% of patients were hospitalized. For 73 patients, both creatinine and urea values were available. Creatinine levels were greater than 3.4 mg/dL (>300 μmol/L) in 27% of patients.

Discussion

We found that the incidence rate of nonfatal ARF was 1.1 cases/10,000 person-years in our study population. Users of NSAIDs had a 3-fold greater risk for developing first-ever ARF than nonusers of NSAIDs in the general population. This risk decreased after treatment was discontinued. Risk was slightly greater with long-term therapy. Although we did not find a clear dose-response relationship, risk was slightly greater among users of a high daily dose. Also, no effect of plasma half-life of

Acknowledgment

The authors thank the GPs for their excellent collaboration and the Boston Collaborative Drug Surveillance Program for providing access to the GPRD.

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: Originally published online as doi:10.1053/j.ajkd.2004.12.005 on January 26, 2005.

: Supported in part by an unrestricted research grant from Pfizer. The design and analysis of this study were made independently by Centro Español de Investigación Farmacoepidemiológica.

View full text

Original investigationsPathogenesis and treatment of kidney disease and hypertensionNonsteroidal anti-inflammatory drugs and risk of ARF in the general population

Section snippets

Data source

Results

Discussion

Acknowledgment

Am J Kidney Dis

Am J Kidney Dis

Am J Med

Analgesic nephropathy

N Engl J Med

Non-steroidal anti-inflammatory drugs and renal function

Br J Rheumatol

Non-steroidal anti-inflammatory drugs and the continuum of renal dysfunction

J Hypertens

Adverse renal effects of anti-inflammatory agentsEvaluation of selective and nonselective cyclooxygenase inhibitors

J Intern Med

Renal toxicity of the nonsteroidal anti-inflammatory drugs

Annu Rev Pharmacol Toxicol

Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs

JAMA

Drug-induced parenchymal renal disease in outpatients

J Clin Pharmacol