amoxicillin-potassium-clavulanate-combination and Jaundice--Obstructive

Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one.. In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy.. One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline.. Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.

Topics: Acute Kidney Injury; Adult; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; beta-Lactamase Inhibitors; Bile; Bilirubin; Biopsy; Chemical and Drug Induced Liver Injury; Creatinine; Drug Therapy, Combination; Hepatitis, Alcoholic; Humans; Hyperbilirubinemia; Jaundice, Obstructive; Kidney Tubules; Liver; Male; Microscopy, Electron; Renal Dialysis; Ultrasonography

Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs.. Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials.. One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI.. AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

Topics: Age Factors; Alanine Transaminase; Alkaline Phosphatase; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Bilirubin; Black or African American; Chemical and Drug Induced Liver Injury; Cholestasis; Cohort Studies; Ethnicity; Female; Hispanic or Latino; Humans; Jaundice; Jaundice, Obstructive; Liver; Male; Middle Aged; Prospective Studies; Registries; Sex Distribution; Time Factors; United States; White People

Topics: Amoxicillin-Potassium Clavulanate Combination; Anesthetics, Inhalation; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Halothane; Humans; Jaundice, Obstructive; Liver Failure, Acute; Liver Transplantation; Postoperative Complications; Sulfonamides; Time Factors