Transplantation outcomes in primary hyperoxaluria

Abstract

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses.

Figure 1

Among PH patients, death censored first kidney allograft survival was better in those who received K+L transplants than K transplantation alone (A). Overall graft survival (B), however, did not differ significantly in K+L compared with K, due to deaths with functioning kidney allografts among the K+L recipients.

Figure 1

Among PH patients, death censored first kidney allograft survival was better in those who received K+L transplants than K transplantation alone (A). Overall graft survival (B), however, did not differ significantly in K+L compared with K, due to deaths with functioning kidney allografts among the K+L recipients.

Figure 2

First kidney allograft survival is improved after 2000 compared to earlier time for PH patients.

Figure 3

Two year survival rates + SE of first kidney allografts of IPHR patients (PH) whose transplants were performed before year 2000 were 59 + 8.7 mean + SE % (95% CI 42–76%, median transplant year 1994, n = 29) compared to 84 + 9.1 % (95% CI 66–100%, median year 2005, n = 29) in 2000 or later. Shown for comparison are USRDS 2 year first kidney graft survival rates for deceased donor (DD) and living donor (LD) kidneys (42).

Figure 4

Delay in the diagnosis of PH until after transplantation, which occurred in 19% of patients (dotted line labeled “Transplant (Tp) before Diagnosis (Dx)”), showed a trend toward earlier kidney allograft loss when compared with those in whom the PH diagnosis was made before transplant (solid line labeled “Tp after Dx”).

Figure 5

Plasma oxalate concentration declined rapidly following successful K+L (A) and K alone (B) transplantation, but remained above normal in most patients during the first year after transplant. The normal range for plasma oxalate levels (< 1.8 μmol/L) is shown in the area shaded gray.

Figure 5

Plasma oxalate concentration declined rapidly following successful K+L (A) and K alone (B) transplantation, but remained above normal in most patients during the first year after transplant. The normal range for plasma oxalate levels (< 1.8 μmol/L) is shown in the area shaded gray.

Figure 6

Urinary oxalate readings (and running average, solid line) from 16 PH recipients of K+L transplants. Normal urine oxalate (<0.46 mmol/1.73m²/24 hrs) is shown by the area shaded gray. Hyperoxaluria persisted in most patients for up to 3 years following transplantation. During the first year, marked hyperoxaluria was characteristic due to mobilization of pre-existing tissue stores of calcium oxalate deposited during renal failure.