Less Is More: A Case of Isolated Kidney Transplantation with Lumasiran in Primary Hyperoxaluria Type 1

Introduction: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of hepatic glyoxylate metabolism. Consequently, it results in the overproduction of oxalate causing nephrolithiasis, nephrocalcinosis, and CKD. In the setting of kidney failure, generally simultaneous liver and kidney transplantation is recommended. Given the pathophysiology with high risk for recurrent allograft involvement and previous lack of effective therapies, there are very few cases of kidney-only transplantations in these patients. We present an exceedingly rare case illustrating the essential role of lumasiran, a small interfering RNA agent, in PH1 kidney-only transplantation. Case Description: A 41 year old male with PH1 and subsequent ESRD, HTN, developmental delay, and history of a resected paraganglioma underwent a deceased kidney donor transplantation. Notably, he developed nephrolithiasis at the age of 13 and underwent lithotripsy at age 26 prior to his PH1 diagnosis. Hemodialysis and lumasiran were initiated three years prior to his transplantation, with plasma oxalate levels ranging between 13-65 mcmol/L during this timeframe. He received alemtuzumab and solumedrol induction with immediate graft function followed by maintenance tacrolimus, mycophenolate, and prednisone. In addition to hyperhydration, low oxalate diet, and pyridoxine, he was continued on his lumasiran injections. Within the first month posttransplantation, his plasma oxalate level became undetectable and creatinine was 0.9. Discussion: PH1 is characterized by a mutation in the alanine glyoxylate aminotransferase gene, which encodes for the hepatic peroxisomal enzyme AGT and results in increased glyoxylate production and thus oxalate. The first drug to treat PH1, lumasiran, was FDA approved in 2020, targeting glycolate oxidase and thereby decreasing oxalate synthesis. Although it does not affect the systemically stored oxalate release, this case highlights the favorable decline in plasma oxalate levels even without prophylactic posttransplantation dialysis that a few cases have employed. This clinical vignette illustrates that patients with PH1 can receive a successful kidney transplant without a concomitant liver transplant in the setting of aggressive medical management, including the novel agent, lumasiran.