Influence of acetaminophen on renal function: a longitudinal descriptive study using a real-world database.

Publisher: Springer Country of Publication: Netherlands NLM ID: 0262521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2584 (Electronic) Linking ISSN: 03011623 NLM ISO Abbreviation: Int Urol Nephrol Subsets: MEDLINE

Publication: Amsterdam : Springer
Original Publication: Budapest, Akademiai Kiadó

Acetaminophen/*pharmacology ; Analgesics, Non-Narcotic/*pharmacology ; Chronic Pain/*drug therapy ; Kidney/*drug effects ; Kidney/*physiology; Acetaminophen/therapeutic use ; Aged ; Aged, 80 and over ; Analgesics, Non-Narcotic/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Creatinine/blood ; Databases, Factual ; Female ; Humans ; Longitudinal Studies ; Male

Purpose: Long-term acetaminophen (APAP) use has poorly defined effects on renal function. We investigated these effects using a real-world database.
Methods: We used a database of health data routinely collected from 185 hospitals serving 20 million patients in Japan. Individuals with chronic pain were selected for the study. The primary outcome was the change in renal function, as measured by 1/serum creatinine (SCr) during the postindex period.
Results: After excluding individuals who did not meet the inclusion criteria, 241,167 patients were included in the analysis (median age 79.0, range 65-101 years; 111,252 were men). APAP was prescribed significantly more frequently to patients with a low renal function (P < 0.001). The annual changes in 1/SCr median and interquartile range (IQR) were - 0.038 (- 0.182 to 0.101) in patients receiving APAP, - 0.040 (- 0.187 to 0.082) in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs), and - 0.025 (- 0.142 to 0.079) in nonmedicated control patients (P < 0.001). These changes were not significantly different among patients with a low renal function, with 0.003 (- 0.066 to 0.113) in the APAP group, 0.000 (- 0.089 to 0.090) in the NSAID group, and - 0.009 (- 0.086 to 0.089) in the control group (P = 0.327).
Conclusion: Physicians tended to select APAP for individuals with a low renal function. The annual changes in 1/SCr were significantly different based on APAP and NSAID use or no analgesia, but the differences were not significant among patients with a low renal function. Overall, long-term use of APAP does not appear to exacerbate the renal function in a clinical setting.

Blantz RC (1996) Acetaminophen: acute and chronic effects on renal function. Am J Kidney Dis 28:S3–6 (PMID: 8669426). (PMID: 10.1016/S0272-6386(96)90561-2)
Ramachandran A, Jaeschke H (2019) Acetaminophen hepatotoxicity. Semin Liver Dis 39:221–234 (PMID: 30849782). (PMID: 10.1055/s-0039-1679919)
Pharmaceuticals and Medical Devices Agency (PMDA). Ethical Drug Search. Pharmaceutical reference of acetaminophen tablets. https://bit.ly/32AxKtT . Accessed 29 Feb 2020.
Fored CM, Ejerblad E, Lindblad P, Fryzek JP, Dickman PW, Signorello LB, Lipworth L, Elinder CG, Blot WJ, McLaughlin JK, Zack MM, Nyrén O (2001) Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 345:1801–1808 (PMID: 11752356). (PMID: 10.1056/NEJMoa010323)
Ucar F, Taslipinar MY, Alp BF, Aydin I, Aydin FN, Agilli M, Toygar M, Ozkan E, Macit E, Oztosun M, Cayci T, Ozcan A (2013) The effects of N-acetylcysteine and ozone therapy on oxidative stress and inflammation in acetaminophen-induced nephrotoxicity model. Ren Fail 35:640–647 (PMID: 23560513). (PMID: 10.3109/0886022X.2013.780530)
Ahmad ST, Arjumand W, Nafees S, Seth A, Ali N, Rashid S, Sultana S (2012) Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol Lett 208:149–161 (PMID: 22093918). (PMID: 10.1016/j.toxlet.2011.10.023)
Yu YL, Yiang GT, Chou PL, Tseng HH, Wu TK, Hung YT, Lin PS, Lin SY, Liu HC, Chang WJ, Wei CW (2014) Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation. Mol Med Rep 9:2077–2084 (PMID: 24682227). (PMID: 10.3892/mmr.2014.2085)
Mazer M, Perrone J (2008) Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 4:2–6 (PMID: 18338302). (PMID: 10.1007/BF03160941)
O'Riordan A, Brummell Z, Sizer E, Auzinger G, Heaton N, O'Grady JG, Bernal W, Hendry BM, Wendon JA (2011) Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity. Nephrol Dial Transplant 26:3501–3508 (PMID: 21652548). (PMID: 10.1093/ndt/gfr050)
Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiodt FV, Ostapowicz G, Shakil AO, Lee WM (2005) Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 42:1364–1372 (PMID: 16317692). (PMID: 10.1002/hep.20948)
Prescott LF (1983) Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs 25:290–314 (PMID: 6343056). (PMID: 10.2165/00003495-198325030-00002)
Kato H, Fujigaki Y, Inoue R, Asakawa S, Shin S, Shima T, Furunishi J, Higaki M, Tanemoto M, Yamaguchi Y, Hoshimoto K, Uozaki H, Uchida S (2014) Therapeutic dose of acetaminophen as a possible risk factor for acute kidney injury: learning from two healthy young adult cases. Intern Med 53:1531–1534 (PMID: 25030567). (PMID: 10.2169/internalmedicine.53.1502)
Hiragi S, Yamada H, Tsukamoto T, Yoshida K, Kondo N, Matsubara T, Yanagita M, Tamura H, Kuroda T (2018) Acetaminophen administration and the risk of acute kidney injury: a self-controlled case series study. Clin Epidemiol 10:265–276 (PMID: 29563839). (PMID: 10.2147/CLEP.S158110)
Kelkar M, Cleves MA, Foster HR, Hogan WR, James LP, Martin BC (2012) Acute and chronic acetaminophen use and renal disease: a case-control study using pharmacy and medical claims. J Manag Care Pharm 18:234–246 (PMID: 22468732). (PMID: 10.18553/jmcp.2012.18.3.234)
Perneger TV, Whelton PK, Klag MJ (1994) Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 331:1675–1679 (PMID: 7969358). (PMID: 10.1056/NEJM199412223312502)
Huerta C, Castellsague J, Varas-Lorenzo C, Garcia Rodriguez LA (2005) Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis 45:531–539 (PMID: 15754275). (PMID: 10.1053/j.ajkd.2004.12.005)
Gooch K, Culleton BF, Manns BJ, Zhang J, Alfonso H, Tonelli M, Frank C, Klarenbach S, Hemmelgarn BR (2007) NSAID use and progression of chronic kidney disease. Am J Med 120(280):e1–280.e7 (PMID: 17349452).
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992 (PMID: 19339088). (PMID: 10.1053/j.ajkd.2008.12.034)
Kawaguchi Y (1999) National comparisons: optimal peritoneal dialysis outcomes among Japanese patients. Perit Dial Int 19:S9–16 (PMID: 10433547). (PMID: 10.1177/089686089901903S03)
Rule AD, Torres VE, Chapman AB, Grantham JJ, Guay-Woodford LM, Bae KT, Klahr S, Bennett WM, Meyers CM, Thompson PA, Miller JP (2006) CRISP Consortium. Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort. J Am Soc Nephrol 17:854–862 (PMID: 16452494). (PMID: 10.1681/ASN.2005070697)

Keywords: Acetaminophen; Longitudinal study; Real-world database; Renal function

0 (Analgesics, Non-Narcotic)
0 (Anti-Inflammatory Agents, Non-Steroidal)
362O9ITL9D (Acetaminophen)
AYI8EX34EU (Creatinine)

Date Created: 20200815 Date Completed: 20210715 Latest Revision: 20210715

20240829

10.1007/s11255-020-02596-7

32794116