Recurrent oxalosis in a combined liver‐kidney transplant patient with primary hyperoxaluria type 1 resulting in graft failure

Abstract

Primary hyperoxaluria (PH) refers to a group of rare autosomal recessive disorders that result in overproduction of oxalate, primarily by the liver. Primary hyperoxaluria type 1 (PH1) is the most common and severe form. 1 Supportive measures may slow the progression of kidney disease, but many patients progress to end stage kidney disease (ESKD). 2 Combined liver-kidney transplantation (CLK) is the treatment of choice; however, outcomes are inferior when transplants are performed later in disease course, with higher total body burden of oxalosis. 3 A 65 year old male developed ESKD in 1998 and underwent deceased-donor kidney transplantation in 2011. The graft failed within 1 year and he was subsequently diagnosed with PH1. Genetic analysis identified two heterozygote pyridoxine-sensitive mutations in the AGXT gene. The patient returned to haemodialysis for 5 years then presented to our unit for CLK. Aiming to prevent early disease recurrence, continuous renal replacement therapy (CRRT) was performed during surgery, followed by daily CRRT for 9 days, then daily intermittent haemodialysis for a further week. Liver allograft function was achieved, however the kidney experienced delayed graft function. Renal biopsy showed acute tubular necrosis and after a further week of dialysis, spontaneous kidney function was evident, and dialysis ceased. On day 29, creatinine was 202 μmol/L and a renal biopsy revealed focal oxalate crystal deposition in 10% of the sample. Repeat biopsy at day 39 showed progressive oxalate deposition. Daily haemodialysis was reinstituted; pyridoxine was administered due to poor oral intake and malnutrition during hospitalization and tacrolimus targets were reduced to 5-8 ng/mL. He was slowly weaned off dialysis at day 65. One year later, he maintains graft function with a creatinine of 300 μmol/L.Evidence surrounding transplantation for PH are limited to small case series and registry data. A retrospective study of 33 CLK recipients showed no recurrence of hyperoxaluria, although those patients were younger, had a much shorter pre-transplant dialysis time and perioperative treatment regimens were not standardized. 4 Patients who are dialysisdependent for several years may have a systemic burden of oxalate, 5 which can persist for several months following CLK despite restoration of oxalate metabolism by the transplanted liver. Estimating total body oxalate burden is extremely difficult and imprecise. Strategies to reduce the oxalate burden are difficult, including low-oxalate diet, low-oxalate Total Parenteral Nutrition (TPN) and intensive dialysis, and must be empirically applied. Awareness of risk of recurrence is critical. A method to measure oxalate burden is urgently required.A 41-year-old man presented with an acute kidney injury, creatinine 685 μmol/L, on a background of diet-controlled type two diabetes mellitus. Renal function 6 months prior was normal, creatinine 90 μmol/L. There was no history of recent illness or dehydration and no symptoms or family history of autoimmune disease. He...

Combined liver kidney transplantation for primary hyperoxaluria type 1: Will there still be a future? Current transplantation strategies and monocentric experience

“…In a median follow-up of 7 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] years after transplantation, no child died and no liver graft failure was observed. Two kidney grafts (33%) were lost early after CLKT, the first due to primary nonfunction, possibly caused by the long ischemia time, the second one after 21 days due to early renal oxalate accumulation, despite a very aggressive HD protocol started immediately after transplantation.…”

“…Four children (67%) were boys; the median age was 11 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The trend of plasma oxalate (Figure 1) was characterized by a quick reduction within 48 hours from renal graft reperfusion as well as after a HD procedure, with plasma oxalate significantly lower than its pre-transplantation levels (p = .027). In small children, even with an intensive hemodialysis schedule with daily sessions, sometimes complemented with peritoneal dialysis overnight, pre-dialysis plasma oxalate was rarely lower than 75 μmol/L, even if after dialysis it dropped to lower than 20 μmol/L.…”

“…In the last decade, the debate has focused on choosing the right approach between simultaneous CLKT 10 and sequential surgical procedures. 11,12 It is well recognized that kidney transplantation alone may result in a dramatic disease recurrence and graft failure 13 ; therefore, kidney substitutive therapy through transplantation is usually planned once the enzyme defect has been obviated, previously or simultaneously, thanks to a liver transplant. Even following this approach, kidney graft loss due to massive oxalate accumulation is a major complication of CLKT, 7,8,10 in up to 50% of cases, despite the adoption of aggressive post-transplant HD protocols.…”

“…Median [IQR] recipient's age at transplantation was 11 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] years; in all cases, a compatible graft from a pediatric brain-dead donor aged 8 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] years was used. In a median follow-up of 7 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] years after combined liver-kidney transplantation, no child died and no liver graft failure was observed; three kidney grafts were lost, due to chronic rejection, primary non-function, and early renal oxalate accumulation. Liver and kidney graft survival remained stable at 1, 3, and 5 years, at 100% and 85%, respectively.…”