Abstract
Background
Acute renal failure is a recognized complication of acute acetaminophen overdose. Its detection depends on rising creatinine concentrations, which is an insensitive method. The present study examined whether proteinuria might correspond with the extent of acute acetaminophen exposure as a possible early marker of renal effects.
Methods
A prospective case-control study included patients attending the emergency department within 24 hours of acetaminophen ingestion. A urine specimen was collected within 12 hours of hospital attendance for creatinine, albumin, and protein determination. Equivalent 4-hour acetaminophen concentrations were used to indicate drug exposure: mild if <100 g/L (<662 mmol/L), moderate if 100–200 g/L (662–1323 mmol/L), or severe if > 200 g/L (> 1323 mmol/L). Data are presented as median interquartile range) and groups compared using Mann Whitney and chi-square tests.
Results
Seventy patients were studied (17 men, 53 women), age 37 years (23–45 years). The stated acetaminophen dose was 15 g (8–20 g), and interval between ingestion and presentation was 4.6 hours (4.1–7.9 hours). Urinary albumin concentrations were 8 mg/L (0–12 mg/L) in the mild group, 12 mg/L (5–25 mg/L) in the moderate group, and 11 mg/L (6–22 mg/L) in the severe group. Total protein concentrations were 90 mg/L (50–183 mg/L), 70 mg/L (40 to 130 mg/L), and 110 mg/L (75–205 mg/L), respectively. The proportions of patients who had urine albumin:creatinine ratio > 3 mg/mmol were 20.8%, 23.5%, and 21.2%, respectively. None of the patients developed acute renal failure.
Conclusions
No relationship was found between the extent of acute acetaminophen exposure and proteinuria. Further work is required to examine whether urinary protein excretion is altered in patients who subsequently develop acute renal failure following acetaminophen overdose.
Keywords: acetaminophen, albumin:creatinine ratio, creatinine, proteinuria, renal failure
Full Text
The Full Text of this article is available as a PDF (116.5 KB).
References
- 1.Waring WS, Jamie H, Leggett GE. Delayed onset of acute renal failure after significant paracetamol overdose: a case series.Hum Exp Toxicol [in press] [DOI] [PubMed]
- 2.Boutis K, Shannon M. Nephrotoxicity after acute severe acetaminophen poisoning in adolescents. J Toxicol/Clin Toxicol. 2001;39:441–445. doi: 10.1081/clt-100105413. [DOI] [PubMed] [Google Scholar]
- 3.Eguia L, Materson BJ. Acetaminophen-related acute renal failure without fulminant liver failure. Pharmacotherapy. 1997;17:363–370. [PubMed] [Google Scholar]
- 4.Kleinman JG, Breitenfield RV, Roth DA. Acute renal failure associated with acetaminophen ingestion: report of a case and review of the literature. Clin Nephrol. 1980;14:201–205. [PubMed] [Google Scholar]
- 5.von Mach MA, Hermanns-Clausen M, Koch I, Hengstler JG, Lauterbach M, Kaes J, et al. Experiences of a poison center network with renal insufficiency in acetaminophen overdose: an analysis of 17 cases. Clin Toxicol. 2005;43:31–37. doi: 10.1081/clt-44992. [DOI] [PubMed] [Google Scholar]
- 6.Bray GP, Mowat C, Muir DF, Tredger JM, Williams R. The effect of chronic alcohol intake on prognosis and outcome in paracetamol overdose. Hum Exp Toxicol. 1991;10:435–438. doi: 10.1177/096032719101000612. [DOI] [PubMed] [Google Scholar]
- 7.Mour G, Feinfeld DA, Caraccio T, McGuigan M. Acute renal dysfunction in acetaminophen poisoning. Ren Fail. 2005;27:381–383. [PubMed] [Google Scholar]
- 8.Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–212. doi: 10.1186/cc2872. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Coca SG, Yalavarthy R, Concato J, Parikh CR. Biomarkers for the diagnosis and risk stratification of acute kidney injury: A systematic review. Kidney Int. 2008;73:1008–1016. doi: 10.1038/sj.ki.5002729. [DOI] [PubMed] [Google Scholar]
- 10.Mitić-Zlatković M, Stefanović V. Acute effects of acetaminophen on renal function and urinary excretion of some proteins and enzymes in patients with kidney disease. Ren Fail. 1999;21:525–532. doi: 10.3109/08860229909045192. [DOI] [PubMed] [Google Scholar]
- 11.Kocaoĝlu S, Karan A, Berkan T, Basşdemir G. Acute acetaminophen nephrotoxicity and urinary gamma-glutamyl transferase activity in rats. Drug Metabol Drug Interact. 1997;14:47–54. doi: 10.1515/dmdi.1997.14.1.47. [DOI] [PubMed] [Google Scholar]
- 12.Bernard AM, de Russis R, Amor AO, Lauwerys RR. Potentiation of cadmium nephrotoxicity by acetaminophen. Arch Toxicol. 1988;62:291–294. doi: 10.1007/BF00332489. [DOI] [PubMed] [Google Scholar]
- 13.Buckley N, Eddleston M. Paracetamol (acetaminophen) poisoning. Clin Evid. 2005;14:1738–1744. [PubMed] [Google Scholar]
- 14.Redon J, Morales-Olivas F, Galgo A, Brito MA, Mediavilla J, Marín R, et al. Urinary albumin excretion and glomerular filtration rate across the spectrum of glucose abnormalities in essential hypertension. J Am Soc Nephrol. 2006;17(12):S236–245. doi: 10.1681/ASN.2006080920. [DOI] [PubMed] [Google Scholar]
- 15.Waring WS, Robinson OD, Stephen AF, Dow MA, Pettie JM. Does the patient history predict hepatotoxicity after acute paracetamol overdose. QJM. 2008;101:121–125. doi: 10.1093/qjmed/hcm139. [DOI] [PubMed] [Google Scholar]
- 16.Jones AF, Vale JA. Paracetamol poisoning and the kidney. J Clin Pharm Ther. 1993;18:5–8. doi: 10.1111/j.1365-2710.1993.tb00560.x. [DOI] [PubMed] [Google Scholar]
- 17.Slitt AL, Dominick PK, Roberts JC, Cohen SD. Standard of care may not protect against acetaminophen-induced nephrotoxicity. Basic Clin Pharmacol Toxicol. 2004;95:247–248. doi: 10.1111/j.1742-7843.2004.pto950508.x. [DOI] [PubMed] [Google Scholar]
- 18.Möller-Hartmann W, Siegers CP. Nephrotoxicity of paracetamol in the rat—mechanistic and therapeutic aspects. J Appl Toxicol. 1991;11:141–146. doi: 10.1002/jat.2550110213. [DOI] [PubMed] [Google Scholar]
- 19.Lorz C, Justo P, Sanz A, Subirá D, Egido J, Ortiz A. Paracetamol-induced renal tubular injury: a role for ER stress. J Am Soc Nephrol. 2004;15:380–389. doi: 10.1097/01.ASN.0000111289.91206.B0. [DOI] [PubMed] [Google Scholar]
- 20.Lorz C, Justo P, Sanz AB, Egido J, Ortíz A. Role of Bcl-xL in paracetamol-induced tubular epithelial cell death. Kidney Int. 2005;67:592–601. doi: 10.1111/j.1523-1755.2005.67115.x. [DOI] [PubMed] [Google Scholar]
- 21.Isik B, Bayrak R, Akcay A, Sogut S. Erdosteine against acetaminophen induced renal toxicity. Mol Cell Biochem. 2006;287:185–191. doi: 10.1007/s11010-005-9110-6. [DOI] [PubMed] [Google Scholar]
- 22.Younes M, Sause C, Siegers CP, Lemoine R. Effect of deferrioxamine and diethyldithiocarbamate on paracetamol-induced hepatoand nephrotoxicity. The role of lipid peroxidation. J Appl Toxicol. 1988;8:261–265. doi: 10.1002/jat.2550080407. [DOI] [PubMed] [Google Scholar]
- 23.Waring WS, Stephen AF, Malkowska AM, Robinson OD. Acute acetaminophen overdose is associated with dose-dependent hypokalaemia: a prospective study of 331 patients. Basic Clin Pharmacol Toxicol. 2008;102:325–328. doi: 10.1111/j.1742-7843.2007.00176.x. [DOI] [PubMed] [Google Scholar]
- 24.Kim YC, Yim HK, Jung YS, Park JH, Kim SY. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: role of male sex hormone. Toxicol Appl Pharmacol. 2007;223:56–65. doi: 10.1016/j.taap.2007.05.009. [DOI] [PubMed] [Google Scholar]
- 25.Trumper L, Monasterolo LA, Elías MM. Nephrotoxicity of acetaminophen in male Wistar rats: role of hepatically derived metabolites. J Pharmacol Exp Ther. 1996;279:548–554. [PubMed] [Google Scholar]
- 26.Abraham P, Kanakasabapathy I, Dian BJ. Propylthiouracil attenuates acetaminophen-induced renal damage in the rat. Nephrology. 2005;10:588–593. doi: 10.1111/j.1440-1797.2005.00494.x. [DOI] [PubMed] [Google Scholar]
- 27.Yamada T, Ludwig S, Kuhlenkamp J, Kaplowitz N. Direct protection against acetaminophen hepatotoxicity by propylthiouracil. J Clin Invest. 1981;67:688–695. doi: 10.1172/JCI110084. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Herget-Rosenthal S, Poppen D, Hüsing J, Marggraf G, Pietruck F, Jakob HG, et al. Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. Clin Chem. 2004;50:552–528. doi: 10.1373/clinchem.2003.027763. [DOI] [PubMed] [Google Scholar]