Correspondence

Preemptive Liver Transplantation from a Living Related Donor for Primary Hyperoxaluria Type I

N Engl J Med 1998; 338:1924June 25, 1998

Article

To the Editor:

Primary hyperoxaluria type I is an autosomal recessive disorder characterized by a deficiency of liver-specific peroxisomal alanine–glyoxylate aminotransferase (EC 2.6.1.44). The disease leads to increased urinary excretion of oxalate, causing urolithiasis, nephrocalcinosis, progressive renal insufficiency, and eventually, oxalosis — that is, the accumulation of insoluble oxalate throughout the body.

The interval between the onset of symptoms and the development of end-stage renal failure varies. Although optimal conservative therapy can delay end-stage renal failure, it usually cannot prevent it. Kidney transplantation to correct end-stage renal failure is frequently followed by recurrence of the disease in the transplanted kidney. Since the liver is the site of the metabolic defect, liver transplantation replaces both the enzyme and the gene. Watts et al. attempted simultaneous liver and kidney grafting to correct the metabolic defect and end-stage renal failure in 1984,1 and this attempt was followed by similar procedures at other transplantation centers.2,3 Liver transplantation alone, from cadaveric donors, before serious renal damage occurs has been successful in some children. I describe a 22-month-old child with primary hyperoxaluria type I who received a liver transplant from a living related donor, her father. Eight months after transplantation and despite the use of nephrotoxic tacrolimus-based immunosuppressive therapy, her kidney function was stable, without the need for dialysis or kidney transplantation.

The patient presented at five weeks of age with dehydration, uremia, and nephrocalcinosis (as shown by ultrasound examination). A kidney biopsy demonstrated oxalate crystals. Laboratory testing when she was nine months old revealed the following results: urine oxalate, 80.5 mg per 24 hours (normal range, 13 to 38); urine oxalate:creatinine ratio, 0.44; blood urea nitrogen, 25 mg per deciliter; serum creatinine, 1.0 mg per deciliter; and corrected glomerular filtration rate, 27 ml per minute. When she was 22 months old, with a body weight of 11 kg, she received a liver transplant from her father. The donor underwent standard left lateral segmentectomies (segments 2 and 3); the weight of the transplanted liver was 320 g. The patient's postoperative course was uneventful except for an episode of mild rejection, which was successfully treated with steroids. Post-transplantation immunosuppressive therapy consisted of prednisone, azathioprine, and tacrolimus (range of serum tacrolimus levels, 8 to 13 mg per milliliter). A kidney biopsy at the time of transplantation revealed moderate-to-severe oxalosis. Eight months after transplantation, the urine oxalate concentration was normal (13.5 mg per 24 hours), the urine oxalate:creatinine ratio was 0.16, the blood urea nitrogen concentration was 9 mg per deciliter, the serum creatinine concentration was 0.9 mg per deciliter, and the corrected glomerular filtration rate was 37 ml per minute.

This case report demonstrates that preemptive liver transplantation from a living related donor for primary hyperoxaluria type I can be accomplished without an immediate impairment in kidney function or the need for dialysis, despite the use of nephrotoxic tacrolimus-based immunosuppressive therapy. Even though there were oxalate deposits in the patient's kidneys before transplantation, eight months after transplantation her kidney function had not deteriorated further. Preemptive liver transplantation from a living related donor eliminates the long waiting time and thus the ongoing kidney damage associated with cadaveric donor transplantation and should therefore be considered for children with primary hyperoxaluria type I.

Rainer W. Gruessner, M.D., Ph.D.
University of Minnesota, Minneapolis, MN 55455

3 References

1. 1

   Watts RW, Calne RY, Williams R, et al. Primary hyperoxaluria (type I): attempted treatment by combined hepatic and renal transplantation. Q J Med 1985;57:697-703
   Web of Science | Medline

2. 2

   Scheinman JI, Alexander M, Campbell ED, Chan JC, Latta K, Cochat P. Transplantation for primary hyperoxaluria in the USA. Nephrol Dial Transplant 1995;10:Suppl 8:42-46
   Web of Science | Medline

3. 3

   Jamieson NV. The European Primary Hyperoxaluria Type I Transplant Registry report on the results of combined liver/kidney transplantation for primary hyperoxaluria 1984-1994. Nephrol Dial Transplant 1995;10:Suppl 8:33-37
   Web of Science | Medline

Citing Articles (11)

Citing Articles

1. 1

   Patrick Niaudet. (2010) Living donor kidney transplantation in patients with hereditary nephropathies. Nature Reviews Nephrology 6:12, 736-743
   CrossRef

2. 2

   (2005) Concurrent or sequential liver and kidney transplantation in children with primary hyperoxaluria type 1?. Pediatric Transplantation 9:6, 693-696
   CrossRef

3. 3

   Markus J. Kemper. (2005) The role of preemptive liver transplantation in primary hyperoxaluria type 1. Urological Research 33:5, 376-379
   CrossRef

4. 4

   Nicholas Onaca, Edmund Q. Sanchez, Larry B. Melton, George J. Netto, Karl A. Glastad, Patriciu A. Martin, Takehisa Ueno, Marlon F. Levy, Robert M. Goldstein, Goran B. Klintmalm. (2005) Cadaveric Orthotopic Auxiliary Split Liver Transplantation and Kidney Transplantation: An Alternative for Type 1 Primary Hyperoxaluria. Transplantation 80:3, 421-424
   CrossRef

5. 5

   Neville V. Jamieson. (2005) A 20-Year Experience of Combined Liver/Kidney Transplantation for Primary Hyperoxaluria (PH1): The European PH1 Transplant Registry Experience 1984–2004. American Journal of Nephrology 25:3, 282-289
   CrossRef

6. 6

   James F. Trotter, Paul H. Hayashi, Igal Kam. 2005. Donor and Recipient Evaluation and Selection for Adult-to-Adult Right Hepatic Lobe Liver Transplantation. , 655-674.
   CrossRef

7. 7

   Maria T. Millan, William E. Berquist, Sam K. So, Minnie M. Sarwal, Karen I. Wayman, Kenneth L. Cox, Guido Filler, Oscar Salvatierra, Carlos O. Esquivel. (2003) One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience1. Transplantation 76:10, 1458-1463
   CrossRef

8. 8

   Debora Kogan-Liberman, Sukru Emre, Benjamin L. Shneider. (2002) Recent advances in pediatric liver transplantation. Current Gastroenterology Reports 4:1, 84-97
   CrossRef

9. 9

   Benjamin L. Shneider. (2002) Pediatric liver transplantation in metabolic disease: Clinical decision making. Pediatric Transplantation 6:1, 25-29
   CrossRef

10. 10

    Daniela Nolkemper, Markus J. Kemper, Martin Burdelski, Irith Vaismann, Xavier Rogiers, Christoph E. Broelsch, Rainer Ganschow, Dirk E. Müller-Wiefel. (2000) Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1. Pediatric Transplantation 4:3, 177-181
    CrossRef

11. 11

    Bernd Hoppe, Markus J Kemper, Arend Bökenkamp, Anthony A Portale, Richard A Cohn, Craig B Langman. (1999) Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure. Kidney International 56:1, 268-274
    CrossRef