Renal transplantation: Basic concepts and evolution of therapy

被引:15
作者
Braun, WE [1 ]
机构
[1] Cleveland Clin Fdn, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA
关键词
kidney transplant; immunosuppression; rejection; allograft; hyperacute; cellular; vascular/humoral/accelerated;
D O I
10.1002/jca.10070
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Within the last 5 years, dramatic changes in the area of renal transplantation have occurred. There have been shifts in the dominant types of rejection, and in the types and utilization of immunosuppressants. Hyperacute rejection is now rarely seen, and acute cellular rejection within the first 6 to 12 months has been reduced to about 10%. However, humoral/antibody-mediated rejection has become a more prevalent problem. In the area of immunosuppressants, the ability to reduce acute cellular rejection to about 10% has been achieved through more judicious use of calcineurin inhibitors (cyclosporine and tacrolimus), increased use of mycophenolate mofetil, and the recent introduction of sirolimus (rapamycin). The polyclonal antibody (anti-thymocyte globulin), as well as monoclonal antibodies directed against the alpha chain of CD25 (daclizumab and basilixamab), have added substantially to the improved success of renal allografts. Because of numerous serious toxicities from glucocorticoids and calcineurin inhibitors, particularly cyclosporine, new studies are utilizing calcineurin-free and/or glucocorticoid avoidance or rapid elimination protocols often in combination with a monoclonal antibody and sirolimus. New immunosuppressants such as FTY720 and Campath-1 are also under study. In addition to its use in treating patients with low-level donor-specific antibody before transplantation in order to avoid hyperacute rejection, apheresis is utilized in various combination protocols after transplantation in the management of hum oral/antibody-mediated rejection, in the treatment of hemolytic uremia syndrome that sometimes occurs with calcineurin inhibitors and sirolimus, as well as in the treatment of focal segmental glomerulosclerosis that has a major risk of recurrence in renal transplants. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:141 / 152
页数:12
相关论文
共 75 条
[1]  
Ahsan N, 1999, TRANSPLANTATION, V68, P1865
[2]   Pretreatment with glucocorticoids enhances T-cell effector function: Possible implication for immune rebound accompanying glucocorticoid withdrawal [J].
Almawi, WY ;
Hess, DA ;
Assi, JW ;
Chudzik, DM ;
Rieder, MJ .
CELL TRANSPLANTATION, 1999, 8 (06) :637-647
[3]   Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506 [J].
Andoh, TF ;
Burdmann, EA ;
Fransechini, N ;
Houghton, DC ;
Bennett, WM .
KIDNEY INTERNATIONAL, 1996, 50 (04) :1110-1117
[4]  
[Anonymous], 1994, Lancet, V344, P423
[5]   IMMUNOSUPPRESSION BY GLUCOCORTICOIDS - INHIBITION OF NF-KAPPA-B ACTIVITY THROUGH INDUCTION OF I-KAPPA-B SYNTHESIS [J].
AUPHAN, N ;
DIDONATO, JA ;
ROSETTE, C ;
HELMBERG, A ;
KARIN, M .
SCIENCE, 1995, 270 (5234) :286-290
[6]   REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION BY GLUCOCORTICOIDS IN NORMAL HUMAN LYMPHOCYTES-T [J].
AYANLARBATUMAN, O ;
FERRERO, AP ;
DIAZ, A ;
JIMENEZ, SA .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (05) :1574-1580
[7]   CALCINEURIN ACTIVITY IS ONLY PARTIALLY INHIBITED IN LEUKOCYTES OF CYCLOSPORINE-TREATED PATIENTS [J].
BATIUK, TD ;
PAZDERKA, F ;
HALLORAN, PF .
TRANSPLANTATION, 1995, 59 (10) :1400-1404
[8]  
BIERER B, 1994, RECENT DEV TRANSPLAN, P9
[9]  
BRAUN WE, 1996, PRIMER TRANSPLANTATI, P229
[10]  
BRAUN WE, 1989, CONTEMP ISS NEPHROL, P45