SHOULD LIVER-TRANSPLANTATION BE PERFORMED BEFORE ADVANCED RENAL-INSUFFICIENCY IN PRIMARY HYPEROXALURIA TYPE-1

Primary hyperoxaluria type 1 (PH1) is a rare recessive autosomal inborn error of glyoxylate metabolism leading to oxalate retention, the first target of which is the kidney. The disease is caused by a defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase. Patients with pyridoxine-resistant forms of PH1 usually require organ replacement therapy, i.e. liver transplantation to supply the deficient enzyme and/or kidney transplantation to replace the affected organ. The current experience of the management of PH1 has emphasized two main points: (1) end-stage renal failure must be avoided since it increases dramatically the risk of systemic involvement, (2) the correction of oxalate overproduction and organ overload requires the removal of the host liver. Practical attitudes towards these ideas are difficult to assess and an individualized strategy is therefore required. Isolated kidney transplantation should be limited to adult patients with late-onset and a mild course of the disease. The present experience of combined liver-kidney transplantation was gained mainly in adult patients with severe systemic involvement; the 3-year patient survival rate recently increased to 82%. This figure might be improved if the procedure were performed earlier while the glomerular filtration rate (GFR) is above 25 ml/min per 1.73 m2. Isolated liver transplantation should be considered in carefully selected children with severe forms of pyridoxineresistance (PH1) before GFR has dropped to less than 30 ml/min per 1.73 m2; it seems to be indicated especially in the presence of a rapid decline of GFR in the preceding year. In two young children who underwent isolated liver transplantation in our units 4 years ago, renal function could be stabilized and severe extrarenal involvement prevented.