Isolated kidney transplantation under lumasiran therapy in primary hyperoxaluria type 1: a report of five cases

Abstract

Primary hyperoxaluria type 1 (PH1) is caused by a mutation in the AGXT gene, encoding the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT). Defects in AGT increase glyoxylate and oxalate production, the latter inducing kidney stones and nephrocalcinosis [1, 2]. Symptoms vary from recurrent bilateral kidney stones with moderate chronic kidney disease (CKD) to early kidney failure in infancy [1, 3, 4]. Until recently, the treatment of PH1 was only symptomatic [2], consisting of standard of care (SOC) with intensive hyperhydration, urine alkalinization and conservative CKD management, with the use of pyridoxine in patients with peculiar mutations [5]. Among patients who reach kidney failure, intensive hemodialysis should be performed; however, systemic oxalosis worsens despite intensive dialysis, and bone is the main compartment for oxalate storage. Combined or sequential double liver/kidney transplantation (CLKT) has been traditionally recommended, as kidney transplant (KTx) alone leads to graft loss due to oxalate deposits, except in B6-sensitive forms [6–8]. With such challenging technical procedures and long-term complications of immunosuppressive therapies, patients’ quality of life (QoL) and survival may be significantly impaired [6].