A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature

Özkaya, Ozan; Genç, Gürkan; Bek, Kenan; Süllü, Yüksel

doi:10.3109/0886022x.2010.509830

Cited by 33 publications

(25 citation statements)

References 10 publications

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“…Because of the importance of the specificity of potential biomarkers, we also measured the panel of miRNAs in a cohort of CKD patients. Kidney injury frequently occurs in parallel with liver injury and has been reported to occur in isolation during APAP poisoning 15…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs as potential markers of human drug-induced liver injury

et al. 2011

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New biomarkers of liver injury are required in the clinic and in preclinical pharmaceutical evaluation. Previous studies demonstrate that two liver-enriched microRNAs (miR-122 and miR-192) are promising biomarkers of acetaminophen-induced acute liver injury (APAP-ALI) in mice. We have examined these molecules, for the first time, in humans with APAP poisoning. Serum miR-122 and miR-192 were substantially higher in APAP-ALI patients, compared to healthy controls (median DDCt [25th, 75th percentile]) (miR-122: 1,265 [491, 4,270] and -192 were substantially higher in APAP-ALI patients than CKD patients (miR-122: P < 0.0001; miR-192: P < 0.0004). miR-122 correlated with peak ALT levels in the APAP-ALI cohort (Pearson R 5 0.46, P 5 0.0005), but not with prothrombin time. miR-122 was also raised alongside peak ALT levels in a group of patients with non-APAP ALI. Day 1 serum miR-122 levels were almost 2-fold higher in APAP-ALI patients who satisfied King's College Criteria (KCC), compared to those who did not satisfy KCC, although this did not reach statistical significance (P 5 0.15). Conclusion: This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug-induced liver injury. (HEPATOLOGY 2011;54:1767-1776 T he development of informative biomarkers of drug-induced liver injury (DILI) remains a primary aim in clinical and preclinical settings. The challenge is to develop biomarkers that are stable, that can be rapidly and accurately quantified in standard hospital laboratories, are minimally invasive, tissue specific, and add true diagnostic/prognostic value to detect and monitor the level of a pathogenic insult to the liver.1 The current battery of available biomarkers to assess liver integrity includes circulating protein markers of hepatocellular injury, such as the aminotransferases, markers of liver functional impairment, such as prothrombin time, markers of blood chemistry, and a number of novel mechanistic biomarkers of tissue injury (e.g., cytokeratin-18 and high-mobility group box-1 protein). 2 Deficiencies discovered with current blood-based biomarkers include the unacceptable frequency of false positives/negatives, poor

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Section: Discussionmentioning

confidence: 99%

Circulating microRNAs as potential markers of human drug-induced liver injury

et al. 2011

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“…9 Case studies described APAP-induced renal failure independent of dosage and degree of hepatotoxicity, suggesting that APAP may have a direct nephrotoxic effect. 10–14 We hypothesized that the incidence, characteristics, and outcomes of APAP and ischemic ALF would differ from other etiologies of ALF.…”

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confidence: 99%

Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

Tujios

Hynan

Vázquez

et al. 2015

Clinical Gastroenterology and Hepatology

123

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BACKGROUND & AIMS Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. METHODS We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). RESULTS Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. CONCLUSIONS Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have better outcomes than those with other forms of ALF.

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“…13,14 However, there are many studies reporting PCM nephrotoxicity in absence of hepatotoxicity. 15,17 In view of these discrepancies, the present study was undertaken to investigate the toxic effect of an overdose of PCM (1 g/kg) orally on the liver and kidney of rabbits. Among available animal models for PCM induced hepatotoxicity or nephrotoxicity, the rabbit was chosen for the present study since other animals like rats are not sensitive to PCM toxicity.…”

Section: Discussionmentioning

confidence: 99%

A significant hepatotoxicity associated with paracetamol overdose in the absence of kidney injury in rabbits

Ahmed

2014

Int J Basic Clin Pharmacol

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A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature

Cited by 33 publications

References 10 publications

Circulating microRNAs as potential markers of human drug-induced liver injury

Circulating microRNAs as potential markers of human drug-induced liver injury

Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

A significant hepatotoxicity associated with paracetamol overdose in the absence of kidney injury in rabbits

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