In combination with kidney transplantation in patients with end-stage renal disease, liver transplantation can be used to treat primary hyperoxaluria type 1 (PH1) to correct the metabolic disorder. In most of the cases published worldwide, combined liver and kidney transplantation was performed either with 2 organs from a single deceased donor that were transplanted simultaneously or with organs from different donors that were transplanted sequentially. Our group and others[2, 3] have also gained some experience with preemptive transplantation in patients with PH1 before deterioration to end-stage renal failure. Because of the shortage of organs available for transplantation, living related sequential transplantation using the liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative.[4-8]
Our search of the relevant medical literature yielded 8 reported cases of sequential liver and kidney transplantation (SeqLKT; Table 1); 7 of the 8 patients were infants or small children.[4-8] The aim of this report is to describe our experience with SeqLKT in 2 young adults with PH1.
Table 1. Published World Experience With Living Donor SeqLKT
A 13-year-old boy presented with recurrent nephrolithiasis and was diagnosed with PH1 by DNA analysis, which revealed an A1119T nucleotide change on axon 10. The family was offered the option of preemptive transplantation using a liver lobe from the father. However, the transplantation was put off when the patient's renal function stabilized (creatinine = 1.2 mg/dL, glomerular filtration rate = 84 mL/minute). Four years later, at the age of 17 years, the patient's renal function abruptly deteriorated because of obstructive uropathy in the other (functioning) kidney, and he was started on continuous dialysis. Two years later, his 47-year-old father was assessed and prepared for the donation of his right liver lobe and left kidney. SeqLKT was performed with an interval of 4.5 months between the 2 procedures. The patient continued on dialysis for 3 days a week between the 2 procedures. Both the donor and the recipient had an uneventful postoperative course, except for the need for re-exploration in the patient to control bleeding 1 day after liver transplantation. Thirty-three months after the procedure, the liver and renal allograft function was normal (Fig. 1).
A 17-year-old girl was referred for combined liver and kidney transplantation with a diagnosis of PH1 based on her medical history. This child first presented at the age of 2.5 years at another hospital with bilateral nephrocalcinosis. During the interval until her referral, she underwent several lithotripsy procedures to remove kidney stones from both kidneys. An analysis of the removed urine calculus showed calcium oxalate stones. No genetic analysis for an alanine transaminase AGT mutation was made. At the time of her referral for transplantation, her renal function was already impaired (creatinine = 2.9 mg/dL, glomerular filtration rate = 26 mL/minute). At this stage, we offered the family the option of SeqLKT using her 45-year-old healthy father as the donor for both organs. However, according to a serological evaluation (an enzyme-linked immunosorbent assay), the patient was positive for hepatitis C virus (HCV) with an HCV polymerase chain reaction level of 13,000 IU/mL. A combined protocol of interferon-γ and ribavirin was started. During the period of the antiviral treatment, the patient's renal function deteriorated, and she was started on dialysis. After 12 months of antiviral treatment and 8 months of dialysis, a complete viral response (HCV polymerase chain reaction level < 15 IU/mL) was achieved, and SeqLKT was performed with the right liver lobe and left kidney of the patient's father. The interval between transplants was 22 days. The patient continued on dialysis for 3 days a week between the 2 procedures. The donor's procedure was complicated by a percutaneous subphrenic fluid collection (day 6), which was drained percutaneously and completely resolved. The recipient's transplant procedure was uneventful. The explanted liver specimen showed signs of periportal inflammation without fibrosis. Sixteen months after kidney transplantation, her liver and renal allograft function was normal (Fig. 1), and the patient remained HCV RNA–negative.
Liver transplantation corrects the metabolic enzyme abnormality of PH1 and prevents oxalate accumulation and deposition. Previous reports of kidney transplantation alone in these patients showed early graft loss. Therefore, the currently recommended approach is simultaneous liver and kidney transplantation[1, 6] in order to spare patients the risk of oxalate deposition in the newly grafted kidney.
Although there is extensive worldwide experience with combined liver and kidney transplantation for PH1,[1, 6] published data on SeqLKT are limited and mostly restricted to children.[4-8] Left lateral segmental resection of an adult for transplantation in a small child carries an acceptable risk to the donor, whereas the donation of a right liver lobe for an adult recipient is associated with a significantly higher incidence of complications and death. Thus, the transplantation of a right liver lobe and a kidney from the same donor may seem to be too hazardous for the donor. Nevertheless, the decision to take that risk in our 2 cases was based on 3 considerations. First, the disease had rapidly progressed to renal failure, and a longer dialysis time before transplantation is known to be associated with a high mortality rate. Second, organs from deceased donors are rare in Israel. Third, the risk to the donor in sequential transplantation is independent for each procedure. As such, after recovery from the liver resection and normalization of liver and renal function, the kidney donation should not carry a higher risk than a kidney donation from any other healthy individual.
There is only 1 report of SeqLKT using a living donor that involved a patient with severe systemic oxalosis requiring the amputation of both legs after transplantation. Our 2 recipients had received relatively short dialysis treatments before transplantation, and both made a complete recovery within 1 month and returned to normal activity soon after the procedure. The recommended approach in the literature is to extend the interval between the 2 transplants to allow a reduction in blood oxalate levels via continuous dialysis after liver transplantation. In our 2 patients, who achieved normal liver allograft function within a few days of transplantation, we used a less intense dialysis protocol of 3 times a week between the 2 procedures. Unfortunately, oxalate plasma levels were not available for our patients to better appreciate the oxalate burden before renal transplantation. We have shown that when a kidney from the same living donor is used, the 2 procedures can be performed within a rather short interval of even less than 1 month. No dialysis is required to prevent oxalate deposition in the new renal allograft as long as adequate urine output (>100 cc/hour) is maintained with a liver allograft with metabolically normal function. This approach differs from the recommended strategy of continuing dialysis after combined liver and kidney transplantation using a deceased donor when the liver allograft does not immediately regain normal metabolic function, and the renal allograft may sustain a severe degree of preservation injury associated with acute tubular necrosis.
We conclude that because of the severe organ shortage, living related SeqLKT using the same donor should be carefully considered not only for children but also for young adults with PH1.