Primary hyperoxaluria: The role and timing of liver and kidney transplantation

Abstract

Primary hyperoxaluria is an uncommon metabolic defect resulting from the deficiency of the enzyme alanine-glyoxylate aminotransferase in the liver. Deficiency of the enzyme results in overproduction and increased urinary excretion of oxalate, resulting in renal deposition of oxalate, which manifests as recurrent renal stones and nephrocalcinosis, often leading to renal failure early in life. Renal replacement therapy in the form of dialysis, peritoneal or hemodialysis, is ineffective in clearing oxalate, and the ensuing systemic oxalosis results in the various clinical manifestations of the disease. Several medications like high-dose pyridoxine, orthophosphate, magnesium, glycosaminoglycans, and probiotic oxalobacter and measures to increase urinary output are useful in the management of raised serum oxalate and promoting urinary excretion of oxalate. The isolated kidney transplantation performed for renal failure does not take care of the biochemical defect which lies in the liver, and therefore, overproduction of oxalate and subsequent deposition in tissues continue unabated. Most recent authors advise against isolated kidney transplant for primary hyperoxaluria due to poor graft outcomes and recurrent renal insufficiency. Preemptive isolated liver transplant might be the first option in selected patients before advanced chronic renal failure has occurred, though it is unusual. With the onset of renal disease, combined liver-kidney transplantation serves to correct the metabolic defect as well as the renal failure. Liver-kidney transplant may be performed either simultaneous (immunological benefit) or sequential (biochemical benefit). In the future, advances in gene therapy and increased insight into the pathophysiological course of primary hyperoxaluria raise the hope to change the outlook of this problem with dismal prognosis.