A288 - Diagnostic Dilemma: Acute Encephalopathy from Hyperammonemia in a Kidney-Pancreas Recipient

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Author Block: M. Behara¹, K. Barrett², C. Ferey², N. Costa³, A. F. Thomas³, ¹Nephrology, MedStar Georgetown University Hospital, Washington, DC, ²Pharmacy, MedStar Georgetown University Hospital, Washington, DC, ³Transplant, MedStar Georgetown Transplant Institute, Washington, DC
*Purpose: Altered mental status can occur post-transplant for a variety of reasons, with neurologic complications at reported rates as high as 21%. Typical causes include delirium, infection, or metabolic disturbances. We present a Simultaneous Pancreas-kidney transplant (SPK) recipient with acute hyperammonemia causing altered mental status, in the absence of chronic liver disease.
*Methods: 51-year-old woman with ESRD, T2DM, HTN, and CAD, who underwent SPK. Early postoperative course was complicated by splenic vein thrombosis and anticoagulation-related bleeding. 3 weeks post-transplant, she presented with AMS and seizures; ammonia was 306 µmol/L. Testing for thyroid, electrolyte, and vitamin deficiencies was negative. CT head was normal. CRRT was initiated for hyperammonemia despite stable graft function. Tacrolimus was switched to cyclosporine due to neurotoxicity concerns. 3 weeks after her transplant, she was found to have hydrops of the Gallbladder, and cholecystostomy was done. MRI showed hepatic and splenic iron deposition; liver biopsy confirmed secondary hemosiderosis with mild portal fibrosis. Despite therapy with lactulose, rifaximin, and levocarnitine, hyperammonemia persisted, requiring hemodialysis. Her AMS improved with dialysis. Further testing showed that Urinary orotic acid was high. Sodium phenylbutyrate was initiated, resulting in decreased ammonia, normalization of mental state, and cessation of dialysis. Her course was further complicated by COVID pneumonia and recurrent hyperammonemia. Genetic testing for urea cycle disorders was negative; organic acid analysis revealed elevated p-hydroxyphenyl acetic acid. Small Intestinal Bacterial Overgrowth was suspected; she was treated for H. pylori and was discharged on sodium phenylbutyrate. Later, sodium phenylbutyrate was discontinued.
*Results: Post-transplant hyperammonemia of unclear etiology caused recurrent encephalopathy in this SPK recipient but improved with sodium phenylbutyrate, allowing discontinuation of dialysis
*Conclusions: Post-transplant hyperammonemia is a rare phenomenon that has been described most often in the lung transplant recipient population. Although hyperammonemia has been linked to calcineurin inhibitors in several lung transplant case reports, the mechanism remains largely unknown. Our patient had no clear reason for her hyperammonemia, although immunosuppression and biliary infection could have contributed. Case highlights the significant impact of hyperammonemia-related acute encephalopathy can have on the post-transplant course. Clinicians should be vigilant in testing for this condition and exploring causes such as medication effects, sarcopenia, and urea cycle disorders.