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PURPOSE AND PATIENTS AND METHODS: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alqnine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. RESULTS: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. CONCLUSIONS. A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients., Primary hyperoxaluria type I (PHI) is a genetic disorder characterized by a deficiency of the enzyme alanine:glyoxylate aminotransferase in the liver. The disease is associated with increased production and excretion of oxalate and glycolate, the formation of urinary stones composed on calcium oxalate, and calcium formation within the kidney, leading to kidney failure. In addition, a process referred to as oxalosis develops in which calcium oxalate is deposited throughout the body, resulting in elevated levels of oxalate ions, or charged oxalate molecules. PHI may be managed by vitamin therapy, or combined liver and kidney transplantation. The deficient enzyme is replaced by new liver graft, whereas the function of the kidney is restored by new kidney graft. Nine cases of PHI treated by combined liver and kidney transplantation are reviewed. One patient with oxalosis died shortly after surgery, while another patient died of infection by cytomegalovirus eight weeks after transplantation. A patient with osteodystrophy, or abnormal bone development, died nine months after surgery, whereas another patient with osteodystrophy died 14 months after surgery due to failure of the transplanted kidney, formation of blood clots, and oxalosis. A fifth patient experienced rejection of the kidney graft and died of gastrointestinal bleeding. Four patients who survived 22 to 38 months after their transplants remained free of kidney disease and recovered from oxalosis. These findings show that combined kidney and liver transplantation may be beneficial for patients with PHI, particularly before the development of advanced kidney failure. (Consumer Summary produced by Reliance Medical Information, Inc.)