Acta Pædiatrica ISSN 0803–5253 CLINICAL OBSERVATION Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetaminophen: a case report Marco Zaffanello (marco.zaffanello@univr.it) 1 , Milena Brugnara 1 , Silvia Angeli 1 , Laura Cuzzolin 2 1.Department of Mother-Child and Biology-Genetics, Section of Paediatrics, University of Verona, Verona, Italy 2.Department of Medicine and Public Health, Section of Pharmacology, University of Verona, Verona, Italy Keywords Acetaminophen, Ibuprofen, Kidney failure, Liver disease, Pyrexia Correspondence Marco Zaffanello, MD, Department of Mother-Child and Biology-Genetics, University of Verona, Piazzale L. Scuro, 10, 37134 Verona, Italy. Tel: +39 045 8124387 | Fax: +39 045 8124790 | Email: marco.zaffanello@univr.it Received 9 October 2008; revised 10 December 2008; accepted 15 December 2008. DOI:10.1111/j.1651-2227.2008.01209.x Abstract The combined use of acetaminophen with ibuprofen has long been in clinical use because the target of action of each drug is different and they do not interfere with each other. Appropriate dosing and managing of these drugs do not likely lead to organ toxicity. However, both acetaminophen and ibuprofen can induce liver problems and acute kidney failure, respectively, if administered at high doses. We report the case of a female child, in treatment with both acetaminophen and ibuprofen, administered at therapeutic antipyretic doses in condition of volume depletion, who suffered acute kidney and liver failure. Conclusion: The combined ibuprofen and acetaminophen treatment, even if administered at therapeutic dosages and in a reduced number of doses, may be dangerous in conditions of volume depletion. INTRODUCTION It is generally known that appropriate dosing and managing of acetaminophen and ibuprofen will unlikely cause organ toxicity. However, both drugs can induce acute renal and liver problems if given at high dosages. In the United States, acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute hepatic failure (1). Usually, initial signs of kidney failure are not ob- served until within 2–3 days of becoming acute. Centrilobu- lar hepatic necrosis, hepatic encephalopathy, vomiting and kidney failure become evident after 3–4 days. Complete res- olution may be achieved in 3–4 weeks (2). As regards ibuprofen, individual sensitivity plays an im- portant role. However, the most frequent side effects are related to an amplification of the pharmacological action of the drug (3). At any rate, adverse events are rarely reported. More research has been recommended to draw this con- clusion more firmly concerning major and minor harmful events (4). We report a case of a very young child treated with both acetaminophen and ibuprofen to manage a febrile infec- tion that developed a combined liver and renal adverse reaction. CASE REPORT A 5-year-old female patient was admitted to the hospital because of febrile convulsions and vomiting. The parents claimed that they had not given her any drugs at home. Moreover, they did not report any previous adverse reaction to medications, to acetaminophen in particular or previous hospitalization. Neonatal and familial clinical histories were unremarkable. Clinical and laboratory investigations at admission, during hospitalization and at follow-up are shown in the Table. In the emergency room (1st day), the girl was treated with rectal diazepam to control febrile convulsions. Mild signs of dehy- dration due to vomiting were resolved with oral rehydration solutions. During hospitalization, in order to prevent a re- currence of fever peaks, she was treated with acetaminophen per os (11 mg/kg/dose, two total doses over 5 h). There- after, because of persistent high temperature, ibuprofen per os (5 mg/kg/dose every 8 h, three total doses) was adminis- tered for the first time (2nd day) in alternating regimen with acetaminophen. The following day hyperpyrexia decreased and then disappeared. After six days the girl experienced arterial hypertension. The young patient was treated with antihypertensive drugs (nifedipine, furosemide and finally verapamil), antibiotics (ceftriaxon) and intravenous fluid in- take according to urine output. When the child was admitted to the hospital, the esti- mated glomerular filtration rate (eGFR) was normal, as were C-reactive protein, blood formula and liver enzymes. A dip- stick urine test revealed high specific gravity and keton bod- ies. Blood pressure and pulse rate were normal (day 1). Three days after admission, an EEG showed slow delta– theta and broad voltage waves that were widespread in the posterior regions of both hemispheres and of doubtful significance. After four days, we detected increased levels of liver en- zymes. An ultrasound of the abdomen showed fluids around the liver, hyperechogenic and enlarged kidneys (polo–polar length >97th percentiles). Biochemical investigation dis- closed high serum creatinine and nitrogen levels, normal concentrations of potassium, base excess (1.7 mmol/L) and serum bicarbonate (26.2 mmol/L), low levels of sodium and albumin, high levels of D-dimer (fibrin equivalent units 1.323 μg/L) and fibrinogen (710 mg/dL). Daily diuresis C 2009 The Author(s)/Journal Compilation C 2009 Foundation Acta Pædiatrica/Acta Pædiatrica 1