Rare Report of Simultaneous Liver and Kidney Transplant for Acute Intermittent Porphyria

Introduction: AIP is a rare autosomal dominant disorder of heme biosynthesis characterized by acute porphyric episodes caused by a deficiency of the hydroxymethylbilane synthase (HMBS) enzyme. These episodes present as abdominal pain, autonomic instability, and neurologic dysfunction resulting in AKI. Most patients experience infrequent episodes, while a subset develop relapsing porphyria leading to chronic kidney disease. Liver transplantation has been shown to reduce attacks by decreasing hepatic overproduction of porphyrin metabolites by replacing with HMBS producing hepatocytes. However, in patients with end-stage kidney disease (ESKD) and refractory symptoms, options are limited. Simultaneous liver-kidney transplant (SLKT) offers a comprehensive solution for these patients but has been rarely reported as a cure for AIP. Case Description: A 47-year-old woman with confirmed AIP via HMBS gene mutation experienced recurrent porphyric attacks since adolescence, which progressively worsened despite regular hemin infusions and plasmapheresis. Her urine porphyrins were quantified at 99 uM at age 33 which increased to 665 uM at age 37. She was later started on Givosiran, siRNA against ALA synthetase, reducing the frequency of her attacks but not preventing them. Over time, she developed ESKD from porphyrin-associated nephropathy, worsened by hypertensive crises during attacks, requiring peritoneal dialysis. Due to refractory symptoms and kidney failure, she was listed for SLKT. At the time of transplant, she received simulect induction and was discharged on tacrolimus, cellcept, and prednisone. Her Model for End-Stage Liver Disease (MELD) 3.0 score was elevated to 21 mainly due to her high creatinine (Cr). One month later, she underwent uncomplicated SLKT. Both allografts functioned immediately. She was discharged on tacrolimus, mycophenolate mofetil, and prednisone. 3 month follow up shows excellent liver allograft function with normal synthetic function, and kidney allograft function with Cr 0.9-1.1mg/dl. She has been able to stop givosiran and has had no porphyric attacks since SLKT. Discussion: This case details a rare, successful SLKT for AIP, leading to complete remission of porphyric symptoms and full recovery of kidney function. AIP is among a group of select disorders where combined transplant should be considered for optimal outcomes.