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Risk of Kidney Failure Associated with the Use of Acetaminophen, Aspirin, and Nonsteroidal Antiinflammatory Drugs
Open accessAbstract
BACKGROUND: People who take analgesic drugs frequently may be at increased risk of end-stage renal disease (ESRD), but the extent of this risk remains unclear. METHODS: We studied 716 patients treated for ESRD and 361 control subjects of similar age from Maryland, Virginia, West Virginia, and Washington, D.C. The study participants were interviewed by telephone about their past use of medications containing acetaminophen, aspirin, and other nonsteroidal antiinflammatory drugs (NSAIDs). For each analgesic drug, the average use (in pills per year) and the cumulative intake (in pills) were examined for any association with ESRD. RESULTS: Heavier acetaminophen use was associated with an increased risk of ESRD in a dose-dependent fashion. When persons who took an average of 0 to 104 pills per year were used for reference, the odds ratio of ESRD was 1.4 (95 percent confidence interval, 0.8 to 2.4) for those who took 105 to 365 pills per year and 2.1 (95 percent confidence interval, 1.1 to 3.7) for those who took 366 or more pills per year, after adjustment for race, sex, age, and intake of other analgesic drugs. When persons who had taken fewer than 1000 pills containing acetaminophen in their lifetime were used for reference, the odds ratio was 2.0 (95 percent confidence interval, 1.3 to 3.2) for those who had taken 1000 to 4999 pills and 2.4 (95 percent confidence interval, 1.2 to 4.8) for those who had taken 5000 or more pills. Approximately 8 to 10 percent of the overall incidence of ESRD was attributable to acetaminophen use. A cumulative dose of 5000 or more pills containing NSAIDs was also associated with an increased odds of ESRD (odds ratio, 8.8), but the use of aspirin was not. CONCLUSIONS: People who often take acetaminophen or NSAIDs have an increased risk of ESRD, but not those who often take aspirin.
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“Renal damage is also produced by chronic use of paracetamol; in a case-control study involving 1,077 subjects who frequently took paracetamol, a dose-dependent relationship between heavier paracetamol use and an increased risk of end-stage renal disease was demonstrated (160).”
From Paracetamol: New Vistas of an Old Drug (2006) · cites this paper as [160]
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Turunen, S., 1 3DTech Oy, H. 1., Kaisto, S., Skovorodkin, I., Mironov, V. A., Kalpio, T., Vainio, S. J., Rak‐Raszewska, A., & 4 3D Bioprinting Solutions, 6. K. H. (2018) · AIMS Cell and Tissue Engineering · doi:10.3934/celltissue.2018.3.119 · Cited by 28
Johnson, E. S., Smith, D. H., Thorp, M. L., Yang, X., & Juhaeri, J. (2011) · BMC Nephrology · doi:10.1186/1471-2369-12-17 · Cited by 27
Krähenbühl, S., Brauchli, Y. B., Kummer, O., Bodmer, M., Trendelenburg, M., Drewe, J., & Haschke, M. (2007) · Digestion · doi:10.1159/000111032 · Cited by 27
“Similarly, and in contrast to aspirin and other non-steroidal anti-inflammatory drugs, paracetamol is also safe with regard to the kidney. Although a large case-control study suggested an association between paracetamol intake and end-stage renal failure (relative risk of 2.1 for patients ingesting ≥1 tablet of parace…”
ResultInfluentialMoimier, G., Guy, C., Berthoux, F. C., Beyens, M. N., Ratrema, M., & Ollagnier, M. (2006) · Therapies · doi:10.2515/therapie:2006035 · Cited by 27
Analgesic Abuse in the Elderly
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The role of acetaminophen in the management of patients with osteoarthritis
Shamoon, M., & Hochberg, M. C. (2001) · The American Journal of Medicine · doi:10.1016/s0002-9343(01)00618-0 · Cited by 26
Bilge, U., Şahin, G., Ünlüoğlu, İ., Ipek, M., Durdu, M., & Keskin, A. (2013) · Renal Failure · doi:10.3109/0886022x.2013.801272 · Cited by 26
“Some case control studies have disclosed that the NSAID use increases the risk of progress to the end-stage kidney failure.(13,23,24) The frequent use of NSAIDs is mainly related to joint diseases such as osteoarthritis, resulting from degenerative disorders that become more common with aging.”
BackgroundAnalgesics use and ESRD in younger age: a case-control study
van der Woude, F. J., Heinemann, L. A. J., Graf, H., Lewis, M., Moehner, S., Assmann, A., & Kühl-Habich, D. (2007) · BMC Nephrology · doi:10.1186/1471-2369-8-15 · Cited by 25
Recognition and Management of Systemic Lupus Erythematosus
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Anti-Inflammatory Drugs and the Kidney
House, A. A., Oliveira, S. S., & Ronco, C. (2007) · The International Journal of Artificial Organs · doi:10.1177/039139880703001203 · Cited by 25
“At the moment of admission to the hospital or ICU, careful attention must be paid to completely understand the medical history of the patient and his/her pharmacological log, especially in relation to the consumption of prescription or non-prescription NSAIDs (5).”
BackgroundMuntner, P., Coresh, J., Klag, M. J., Whelton, P. K., & Perneger, T. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.34515 · Cited by 25
Self-citationROLE AND IMPACT OF OVER-THE-COUNTER MEDICATIONS IN THE MANAGEMENT OF HEADACHE
Sheftell, F. D. (1997) · Neurologic Clinics · doi:10.1016/s0733-8619(05)70303-0 · Cited by 25
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“Some case-control studies have found a positive association between aspirin use and CKD prevalence [4, 5], while other studies have found no association [6, 7].”
BackgroundIbrahim, N. H. M., Grégoire, M., Devassy, J. G., Wu, Y., Yoshihara, D., Yamaguchi, T., Nagao, S., & Aukema, H. M. (2014) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2014.10.005 · Cited by 24
Nakano, M., Ueno, M., Nishi, S., Suzuki, S., Hasegawa, H., Watanabe, T., Kuroda, T., Ito, S., & Arakawa, M. (1996) · Annals of the Rheumatic Diseases · doi:10.1136/ard.55.8.520 · Cited by 23
Renal Function in a Rat Model of Analgesic Nephropathy: Effect of Chloroquine
Ahmed, M. H., Ashton, N., & BALMENT, R. J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.047233 · Cited by 23
“4 for cumulative lifetime intake of more than 5000 tablets containing paracetamol (Perneger et al., 1994).”
BackgroundAnalgesic Efficacy and Pharmacokinetics of Ketoprofen Administered into a Surgical Site
Dionne, R. A., Gordon, S. M., Tahara, M., Rowan, J. S., & Troullos, E. S. (1999) · The Journal of Clinical Pharmacology · doi:10.1177/00912709922007679 · Cited by 23
Nonsteroidal anti-inflammatory drugs and the kidney
Stürmer, T., Elseviers, M. M., & Broe, M. E. D. (2001) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200103000-00001 · Cited by 22
Contrasting effects of diclofenac and ibuprofen on active imatinib uptake into leukaemic cells
Wang, J., Hughes, T. P., Kok, C. H., Saunders, V. A., Frede, A., GrootObbink, K., Osborn, M. P., Somogyi, A. A., D’Andrea, R. J., & White, D. L. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.173 · Cited by 22
“…been abundant evidence of DDI between NSAIDs and other co-administrated drugs, which may prolong the plasma elimination and lead to various side effects such as liver damage (Bjorkman, 1998), kidney dysfunction (Perneger et al, 1994), and aggravation of cardiovascular diseases (Farooq et al, 2008).”
BackgroundShukla, A., Rai, M. K., Prasad, N., & Agarwal, V. (2017) · The Nephron journals/Nephron journals · doi:10.1159/000455167 · Cited by 22
Kratz, A. L., Murphy, J. F., Kalpakjian, C. Z., & Chen, P. (2017) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000550 · Cited by 21
Quality Indicators for the Care of Osteoporosis in Vulnerable Elders
Grossman, J., & MacLean, C. H. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01347.x · Cited by 22
Metadata
- Authors
- Perneger, T. V., Whelton, P. K., & Klag, M. J.
- Affiliations
- University of Geneva (CH)
- Johns Hopkins University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1994-12-22
- Volume
- 331
- Issue
- 25
- Pages
- 1675-1679
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2320758398
- Cited by
- 484
- References
- 15
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 18 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 21 · 2019: 19 · 2018: 11 · 2017: 10 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 20
- FWCI
- 20.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agency for Healthcare Research and Quality (R03-HS06978-01)
- National Center for Research Resources (5MOIRR00722, RR 00035)
- Topics
- Health Sciences › Medicine › Nephrology › Nephrotoxicity and Medicinal Plants
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- end-stage renal disease, renal failure, paracetamol, aspirin, nonsteroidal anti-inflammatory drugs, analgesic use, dose-response relationship, attributable risk, drug-induced nephrotoxicity
- MeSH terms
- Acetaminophen, Adult, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Drug Utilization, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Risk Factors, Causality, Confidence Intervals, Odds Ratio, Case-Control Studies
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