Standard of Care may not Protect against Acetaminophen‐Induced Nephrotoxicity

Slitt, Angela L.; Dominick, Pamela K.; Roberts, Jeanette C.; Cohen, Steven D.

doi:10.1111/j.1742-7843.2004.pto950508.x

Cited by 21 publications

(11 citation statements)

References 5 publications

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“…Renal cells are unable to generate glutathione locally from precursors and must obtain glutathione from plasma, perhaps lessening the protective effect of NAC in the kidney. 28 In our study, the use of NAC did not appear to have any impact on renal function; however, more than 90% of APAP-related ALF patients received NAC, so an adequate comparison with patients not receiving NAC could not be made. Potential limitations of our study included the lack of information on kidney status before admission to the study and the lack of urinary volume or sediment data to confirm the presence or absence of tubular damage.…”

Section: Discussioncontrasting

confidence: 56%

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

Tujios

Hynan

Vázquez

et al. 2015

Clinical Gastroenterology and Hepatology

119

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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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Section: Discussioncontrasting

confidence: 56%

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

Tujios

Hynan

Vázquez

et al. 2015

Clinical Gastroenterology and Hepatology

119

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“…Although NAC has not proven to be harmful to the kidney, its role in patients without hepatoxicity and only isolated renal function is uncertain. NAC administered either intraperitoneally or orally to APAP-poisoned mice did not protect against nephrotoxicity [23]. Oral NAC is a very safe therapy, but its utility in these patients is unknown.…”

Section: Management and The Role Of Nacmentioning

confidence: 93%

Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management

2008

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Acetaminophen-induced liver necrosis has been studied extensively, but the extrahepatic manifestations of acetaminophen toxicity are currently not described well in the literature. Renal insufficiency occurs in approximately 1-2% of patients with acetaminophen overdose. The pathophysiology of renal toxicity in acetaminophen poisoning has been attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney, although other mechanisms have been elucidated, including the role of prostaglandin synthetase and N-deacetylase enzymes. Paradoxically, glutathione is considered an important element in the detoxification of acetaminophen and its metabolites; however, its conjugates have been implicated in the formation of nephrotoxic compounds. Acetaminophen-induced renal failure becomes evident after hepatotoxicity in most cases, but can be differentiated from the hepatorenal syndrome, which may complicate fulminant hepatic failure. The role of N-acetylcysteine therapy in the setting of acetaminophen-induced renal failure is unclear. This review will focus on the pathophysiology, clinical features, and management of renal insufficiency in the setting of acute acetaminophen toxicity.Case: A 47-year-old female was found lethargic at home and brought by ambulance to an emergency department. History from family members suggested an inadvertent acetaminophen overdose, and she had last been seen a few hours earlier. She reportedly ingested 18 tablets of 500 mg acetaminophen (APAP) over the previous two days because she had run out of her prescription pain medication. Her past medical history was significant for fibromyalgia, arthritis, and a prior gastric bypass procedure. She had no history of alcohol abuse or renal insufficiency. She was lethargic. Vital signs: BP 128/96 mmHg, pulse 112/min, respirations 32/min; pulse oximetry 98% on 2L nasal cannula oxygen. Laboratory studies: BUN 9 mg/dL, creatinine 0.9 mg/dl, acetaminophen 12 mcg/mL, AST 5409 u/L and ALT 1085 u/L. A urinalysis was negative for blood with trace protein and ketones. A urine drug screen was positive for marijuana and opioid metabolites. At the initial hospital, she was treated with N-acetylcysteine (NAC) orally. Subsequently, she developed fulminant hepatic failure with elevated transaminases, hypoglycemia, and coagulopathy (Tables 1A and 1B). She was transferred

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“…For example, caspase-mediated apoptosis and oxidative stress, which can evoke acute tubular dysfunction and cortical interstitial inflammation 9 , 10. Acetylcysteine administration may not lessen the risk of paracetamol-induced nephrotoxicity, which further emphasises the distinct mechanisms underlying hepatic and renal injury 11. Clinical markers of paracetamol nephrotoxicity have been explored, for example urinary protein concentrations and γ glutamyltransferase activity, but none has been found to offer a reliable early marker of injury 12 , 13…”

Section: Discussionmentioning

confidence: 99%

Onset and recovery of hepatic and renal injury after deliberate acute paracetamol overdose

Waring¹

2009

Case Reports

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A 54-year-old woman presented to hospital after deliberate acute ingestion of paracetamol 20 g. Despite early administration of a standardised acetylcysteine regimen, the patient developed acute liver impairment and acute renal impairment. Prolonged acetylcysteine administration and supportive measures allowed restoration of normal liver and renal function. Early presentation to hospital and prolonged duration of follow-up gave an unusual opportunity to examine the onset and duration of paracetamol-induced hepatic and renal impairment.

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Standard of Care may not Protect against Acetaminophen‐Induced Nephrotoxicity

Cited by 21 publications

References 5 publications

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

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

Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management

Onset and recovery of hepatic and renal injury after deliberate acute paracetamol overdose

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