Bile Cast Nephropathy Following Liver Injury from Ashwagandha

Introduction: Ashwagandha has become a popular herbal supplement in the last decade. At the same time, an increasing number of cases of drug-induced liver injury (DILI) have been reported. Here we present a unique case of biopsy-proven DILI from ashwagandha complicated by biopsy-proven bile cast nephropathy requiring kidney replacement therapy. Case Description: A 70-year-old man with hypertension and coronary artery disease presented with a 1-week history of fatigue and polyuria. He had been taking ashwagandha supplements for the last four months and drank 3-4 alcoholic beverages per week. Vital signs and physical exam were unremarkable. Laboratory analyses were significant for hemoglobin 18.7 g/dL, sodium 124 (corrected 133 mEq/L), glucose 694 mg/dL, creatinine at baseline 1.1 mg/dL, A1c 11.2%, AST 1472 U/L, ALT 1315 U/L, alkaline phosphatase 273 U/L, total bilirubin 2.42 (direct 1.53 mg/dL) and ferritin 37373 ng/mL. Negative dsDNA, ANA, AMA, ASMA. Imaging was unremarkable. Liver biopsy on day 7 showed acute-on-chronic hepatitis with moderate inflammatory activity and periportal fibrosis consistent with drug reaction. He subsequently developed worsening bilirubin (peak 55.2) and AKI. Due to concern for AIN, kidney biopsy was performed on day 14. It showed acute tubular injury with multifocal granular reddish-brown casts with weakly positive bile stain and IgA nephropathy. The patient was started on intermittent HD on day 16 and remains dialysis dependent 50 days later. Discussion: The etiology of liver injury was most certainly ashwagandha as he had not started any recent medications or other supplements. AKI was not a direct effect of ashwagandha as evidenced by histopathology and elevated bilirubin, while IgA nephropathy was likely secondary to liver dysfunction. Despite high ferritin, there was no concern for Still disease or HLH. Although the diagnosis of type 2 diabetes mellitus was new, it is probably unrelated as the A1c suggests greater chronicity.