Late Diagnosis of Primary Hyperoxaluria Type 1 in a Geriatric Patient: Unique Clinical Course with Lumasiran

Introduction: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disease characterized by impaired hepatic glyoxylate metabolism, leading to excess urine oxalate (UOx) and plasma oxalate (POx). PH1 is a major risk factor for calcium oxalate kidney stones, nephrocalcinosis, chronic kidney disease (CKD), and end-stage kidney disease (ESKD). The median age of diagnosis is 8 years. Treatment may include high fluid intake, crystallization inhibitors, pyridoxine, and small interfering RNA (siRNA) agents. In patients with advanced CKD, hemodialysis (HD) is used to prevent systemic oxalosis and serves as a bridge to combined liver-kidney transplantation (CLKT). Case Description: An 83-year-old woman with recurrent calcium oxalate nephrolithiasis and advanced CKD was referred to our kidney stone prevention clinic. She had been initiated on HD one month prior for uremia. She first started passing kidney stones around age 50 and had required multiple stone removal surgeries. Her sister died of CKD of unknown etiology and also suffered from recurrent nephrolithiasis. Five years prior, 24-hour urine was notable for a UOx level of 194 mg (20-40 mg/d). Her POx level is elevated at 34 µmol/L (≤ 2 µmol/L). Kidney stone disorder gene panel testing identified two pathogenic missense variants in the AGXT gene. She was started on pyridoxine and lumasiran resulting in normalization of POx levels six months later. Remarkably, she reduced her HD frequency and ultimately discontinued HD altogether. Discussion: PH1 is a devasting metabolic disease. Patients often suffer from frequent stone episodes and develop advanced CKD requiring intensive HD while awaiting CLKT. This outlook has improved with the advent of siRNA therapies targeting hepatic enzymes, thereby reducing UOx and POx levels. This case features the oldest known age for a PH1 diagnosis and demonstrates the effectiveness of lumasiran, including the unexpected clinical course of discontinuation of HD.