Primary hyperoxaluria, today and tomorrow

Primary hyperoxaluria is a group of rare inherited diseases, often associated with severe systemic involvement, leading to end-stage renal disease and further extrarenal life threatening complications, mainly in patients with early onset. Type 1 is the most common, and is due to a liver-specific peroxisomal alanine-glyoxylate aminotransferase deficiency, so that the kidney must clear excessive amounts of oxalate, leading to nephrocalcinosis and urolithiasis. Along with glomerular filtration rate impairment, insoluble oxalate is progressively stored by all organs, mainly bones. The diagnosis is based on urine oxalate measurement and requires genotyping in order to propose the most appropriate management and allow prenatal diagnosis. Supportive measures (pyridoxine, hydration, crystallization inhibitors) are the cornerstone of early management. However many patients have a delayed diagnosis so that dialysis is mandatory, but any kind of dialysis would have limited benefit since oxalate overproduction by the liver would not be balanced by dialysis. Early (preemptive) combined liver-kidney transplantation is currently the most appropriate treatment but is a challenging procedure. In the next future, promising options such as RNA interference therapy might be an alternative to organ transplantation. Type 2 and type 3 primary hyperoxalurias are less common and have less severe phenotype.