Combined liver kidney transplantation in primary hyperoxaluria type 1

被引:45
作者
Cochat, P [1 ]
Gaulier, JM
Nogueira, PCK
Feber, J
Jamieson, NV
Rolland, MO
Divry, P
Bozon, D
Dubourg, L
机构
[1] Hop Edouard Herriot, Unite Nephrol Pediat, F-69437 Lyon 03, France
[2] Hop Edouard Herriot, Dept Pediat, F-69437 Lyon, France
[3] Univ Lyon 1, F-69365 Lyon, France
[4] Hop Edouard Herriot, Lab Biochim D, Lyon, France
[5] Univ Cambridge, Sch Med, Dept Surg, Cambridge, England
[6] Hop Debrousse, Ctr Etud Malad Metab, Lyon, France
关键词
oxalosis; primary hyperoxaluria; kidney transplantation; liver transplantation; combined liver-kidney transplantation;
D O I
10.1007/PL00014327
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder characterised by an increased urinary excretion of calcium oxalate, leading to recurrent urolithiasis, nephrocalcinosis and accumulation of insoluble oxalate throughout the body (oxalosis) when the glomerular filtration rate falls to below 40-20 mL/min per 1.73 m(2). The disease is due to a functional defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), the gene of which is located on chromosome 2q37.3. The diagnosis is based on increased urinary oxalate and glycollate, increased plasma oxalate and AGT measurement in a liver biopsy. AGT mistargeting may be investigated by immuno-electron microscopy and DNA analysis. End-stage renal failure is reached by the age of 15 years in 50% of PH 1 patients and the overall death rate approximates 30%. The conservative treatment includes high fluid intake, pyridoxine and crystallisation inhibitors. Since the kidney is the main target of the disease, isolated kidney transplantation (Tx) has been proposed in association with vigorous peri-operative haemodialysis in an attempt to clear plasma oxalate at the time of Tx. However, because of a 100% recurrence rate, the average 3-year graft survival is 15%-25% in Europe, with a 5-10-year patient survival rate ranging from 10% to 50%. Since the liver is the only organ responsible for the detoxification of glyoxylate by AGT, deficient host liver removal is the first rationale for enzyme replacement therapy. Subsequent orthotopic liver Tx aims to supply the missing enzyme in its normal cellular and subcellular location and thus can be regarded as a form of gene therapy. Because of the usual spectrum of the disease, isolated liver Tx is limited to selected patients prior to having reached an advanced stage of chronic renal failure. Combined liver-kidney Tx has therefore become a conventional treatment for most PH1 patients: according to the European experience, patient survival approximates 80% at 5 years and 70% at 10 years. In addition, the renal function of survivors remains stable over time, between 40 and 60 ml/min per 1.73 m(2) after 5 to 10 years. In addition, liver Tx may allow the reversal of systemic storage disease (i.e. bone, heart, vessels, nerves) and provide valuable quality of life. Whatever the transplant strategy, the outcome is improved when patients are transplanted early in order to limit systemic oxalosis. According to the European experience, it appears that combined liver-kidney Tx is performed in PH 1 patients with encouraging results, renal Tx alone has little role in the treatment of this disease, and liver Tx reverses the underlying metabolic defect and its clinical consequences.
引用
收藏
页码:S75 / S80
页数:6
相关论文
共 26 条
[1]   Selective renal transplantation in primary hyperoxaluria type 1 [J].
Allen, AR ;
Thompson, EM ;
Williams, G ;
Watts, RWE ;
Pusey, CD .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1996, 27 (06) :891-895
[2]   KIDNEY-TRANSPLANTATION IN PRIMARY OXALOSIS - DATA FROM THE EDTA REGISTRY [J].
BROYER, M ;
BRUNNER, FP ;
BRYNGER, H ;
DYKES, SR ;
EHRICH, JHH ;
FASSBINDER, W ;
GEERLINGS, W ;
RIZZONI, G ;
SELWOOD, NH ;
TUFVESON, G ;
WING, AJ .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 1990, 5 (05) :332-336
[3]  
Cochat P, 1995, Adv Nephrol Necker Hosp, V24, P227
[4]   SHOULD LIVER-TRANSPLANTATION BE PERFORMED BEFORE ADVANCED RENAL-INSUFFICIENCY IN PRIMARY HYPEROXALURIA TYPE-1 [J].
COCHAT, P ;
SCHARER, K .
PEDIATRIC NEPHROLOGY, 1993, 7 (02) :212-218
[5]   EPIDEMIOLOGY OF PRIMARY HYPEROXALURIA TYPE-1 [J].
COCHAT, P ;
DELORAINE, A ;
ROTILY, M ;
OLIVE, F ;
LIPONSKI, I ;
DERIES, N .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 1995, 10 :3-7
[6]  
COCHAT P, 1991, TRANSPLANTATION CLIN, V22, P73
[7]  
COHEN AT, 1991, NESTLE NUTR WORKS SE, V24, P213
[8]  
*COM LITH ASS FRAN, 1996, PROGR UROLOGIE, V6, P955
[9]  
DANPURE CJ, 1991, TRANSPLANT CLIN IMM, V22, P91
[10]  
FLYE MW, 1990, TRANSPLANTATION, V50, P1051