Transplantation for Primary Hyperoxaluria Type 1: Designing New Strategies in the Era of Promising Therapeutic Perspectives

Abstract

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase that results in the overproduction of oxalate. It can be devastating especially for kidneys, leading to end-stage renal disease (ESRD) during the first 2 to 3 decades of life in most patients. Consequently, many PH1 patients need kidney transplantation. However, because PH1 is caused by a liver enzyme deficiency, the only cure of the metabolic defect is liver transplantation. Thus, current transplant strategies to treat PH1 patients with ESRD include dual liver-kidney transplantation. However, the morbidity and mortality associated with liver transplantation make these strategies far from optimal. Fortunately, a therapeutic revolution is looming. Indeed, innovative drugs are being currently tested in clinical trials, and preliminary data show impressive efficacy to reduce the hepatic overproduction of oxalate. Hopefully, with these therapies, liver transplantation will no longer be necessary. However, some patients with progressing renal disease or those who will be diagnosed with PH1 at an advanced stage of chronic kidney disease will ultimately need kidney transplantation. Here we review the current knowledge on this subject and discuss the future of kidney transplant management in PH1 patients in the era of novel therapies.

Keywords: RNA interference drugs; kidney transplantation; liver transplantation; primary hyperoxaluria type 1.