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Five-year results of living related renal donation are similar to cadaveric transplantation in black South Africans
Five-Year Results of Living Related Renal Donation Are Similar to Cadaveric Transplantation in Black South Africans T.P. Thulo, M.C.M. Modiba, A. Kobryn, S. Ndlovu, and P. Becker
R
ESULTS OF RENAL transplantation in blacks are inferior to other racial groups.1 The use of triple therapy including prednisone, azathioprine, and cyclosporine for maintenance and monoclonal or polyclonal antibodies for induction immunosuppression improves the results.2– 6 Factors contributing to the inferior results in blacks include include poor HLA matching, resistance to immunosuppression, noncompliance, and strong pretransplant immune responder status.7–10 Reported experiences in living related donation suggest that transplantation results in blacks are also inferior.11,12 Our previous experience suggested that living related donation improved results in the precyclosporine era in South Africa.13 The aim of this study is to document results of living related as compared to cadaveric donation in South African blacks in the cyclosporine era. METHODS The Ga-Rankuwa Hospital forms part of a Medical University of Southern Africa (MEDUNSA) academic complex situated 31 km to the north of Pretoria in South Africa. From May 1984 to August 2000, 130 renal transplants were performed at MEDUNSA. Of these, 30 were living related. All organs were harvested locally and flushed with Euro-Collin’s solution before storage in ice slush. Although HLA-A, -B, and -DR antigens were identified serologically, results were not used for organ allocation. Panel-reactive antibodies (PRA) were screened while recipients were on the waiting list. Complement-dependent T-cell cross-match was done routinely to determine donor suitability. Mixed lymphocyte cultures were not done. Triple immunosuppression with prednisone, azathioprine, and cyclosporine a was used for maintenance. Acute rejection episodes were treated with three 1-gm pulses of solumedrol and OKT3 or ATG for steroid-resistant rejection.
RESULTS
The median age of the 130 transplant recipients was 32 years (range 7 to 53) and the F:M ratio, 1:1.8. Only two of the 30 living related pairs were HLA-A, -B, and -DR identical. Actuarial graft survival at yearly intervals was 95%, 95%, 95%, 75%, and 60% in living related as compared to 85%, 80%, 75%, 72%, and 50% for cadaveric transplantation. The survival curves (Fig 1) show similar actuarial survival at 5 years (Kaplan-Meier, P ⫽ .9).
Fig 1. Actuarial survival in related living versus cadaveric donation.
The causes of graft loss in living related recipients are shown in Table 1. Chronic rejection was the most common cause of graft loss. Four patients died of septicemic shock and multiple organ failure with functioning renal allografts. One allograft was lost from recurrent oxalosis. DISCUSSION
The results of cadaveric renal transplantation have improved in South African blacks in the cyclosporine era as compared to results reported prior to cyclosporine immunosuppression.13,14 As a result, the beneficial effect of HLA matching by living related kidney donation is limited. Results of living related transplantation may be improved by six antigen (HLA-A, -B, and -DR) matching. Furthermore, where possible, the donor should be chosen according to mixed lymphocyte culture compatibility.14 Identification of HLA antigens using serological methods in blacks results in an unacceptably high number of blanks. We suggest that DNA methods for HLA typing be developed for our black population. From the Department of General Surgery (T.P.T., M.C.M.M., A.K., S.N.) and Medical Research Council (P.B.), Medical University of Southern Africa, South Africa. Address reprint requests to Prof M.C.M. Modiba, Department of General Surgery, PO Box 231, MEDUNSA, 0204, South Africa.
© 2002 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/02/$–see front matter PII S0041-1345(02)03426-7
Transplantation Proceedings, 34, 2565–2566 (2002)
2565
2566
THULO, MODIBA, KOBRYN ET AL
Table 1. Causes of Graft Loss in Living Related Donation Rejection Hyperacute Acute Chronic Death with functioning allografts—septicemia Recurrent disease— oxalosis
1 1 7 4 1
REFERENCES 1. Barger BO, Hudson SL, Shroyer TW, et al: Clin Transpl 217, 1987 2. Koyama H, Cecka JM: Clin Transpl 269, 1991 3. Valente JF, Hariharan S, Peddi VR, et al: Clin Transpl 11:231, 1997
4. Gastron RS, Hudson SL, Deierhoi MH, et al: Transplantation 53:103, 1992 5. Van Buren DH, Richie RE, Nylander W, et al: South Med J 84:715, 1991 6. Raofi V, Holman DM, Coady N, et al: Am J Surg 177:29, 1999 7. Kerman RH, Kimball PM, Van Buren CT, et al: Transplantation 51:338, 1991 8. Butkus DE, Meydrech EF, Raju SS: N Eng J Med 327:840, 1992 9. Sehgal AR: Am J Kidney Dis 35:S148, 2000 10. Koyama H, Cecka JM, Terasaki PI: Transplantation 57: 1064, 1994 11. Cecka JM: Clin Transpl 363, 1995 12. Isaacs RB, Nock SL, Spencer CE, et al: Am J Kidney Dis 34:706, 1999 13. Modiba MCM, Mzamane DVA, Pantanowitz D, et al: Transplant Proc 21:2010, 1988 14. Modiba MCM, Ngcobo TK, Wolf JS, et al: S Afr J Surg 32:99, 1994
R
ESULTS OF RENAL transplantation in blacks are inferior to other racial groups.1 The use of triple therapy including prednisone, azathioprine, and cyclosporine for maintenance and monoclonal or polyclonal antibodies for induction immunosuppression improves the results.2– 6 Factors contributing to the inferior results in blacks include include poor HLA matching, resistance to immunosuppression, noncompliance, and strong pretransplant immune responder status.7–10 Reported experiences in living related donation suggest that transplantation results in blacks are also inferior.11,12 Our previous experience suggested that living related donation improved results in the precyclosporine era in South Africa.13 The aim of this study is to document results of living related as compared to cadaveric donation in South African blacks in the cyclosporine era. METHODS The Ga-Rankuwa Hospital forms part of a Medical University of Southern Africa (MEDUNSA) academic complex situated 31 km to the north of Pretoria in South Africa. From May 1984 to August 2000, 130 renal transplants were performed at MEDUNSA. Of these, 30 were living related. All organs were harvested locally and flushed with Euro-Collin’s solution before storage in ice slush. Although HLA-A, -B, and -DR antigens were identified serologically, results were not used for organ allocation. Panel-reactive antibodies (PRA) were screened while recipients were on the waiting list. Complement-dependent T-cell cross-match was done routinely to determine donor suitability. Mixed lymphocyte cultures were not done. Triple immunosuppression with prednisone, azathioprine, and cyclosporine a was used for maintenance. Acute rejection episodes were treated with three 1-gm pulses of solumedrol and OKT3 or ATG for steroid-resistant rejection.
RESULTS
The median age of the 130 transplant recipients was 32 years (range 7 to 53) and the F:M ratio, 1:1.8. Only two of the 30 living related pairs were HLA-A, -B, and -DR identical. Actuarial graft survival at yearly intervals was 95%, 95%, 95%, 75%, and 60% in living related as compared to 85%, 80%, 75%, 72%, and 50% for cadaveric transplantation. The survival curves (Fig 1) show similar actuarial survival at 5 years (Kaplan-Meier, P ⫽ .9).
Fig 1. Actuarial survival in related living versus cadaveric donation.
The causes of graft loss in living related recipients are shown in Table 1. Chronic rejection was the most common cause of graft loss. Four patients died of septicemic shock and multiple organ failure with functioning renal allografts. One allograft was lost from recurrent oxalosis. DISCUSSION
The results of cadaveric renal transplantation have improved in South African blacks in the cyclosporine era as compared to results reported prior to cyclosporine immunosuppression.13,14 As a result, the beneficial effect of HLA matching by living related kidney donation is limited. Results of living related transplantation may be improved by six antigen (HLA-A, -B, and -DR) matching. Furthermore, where possible, the donor should be chosen according to mixed lymphocyte culture compatibility.14 Identification of HLA antigens using serological methods in blacks results in an unacceptably high number of blanks. We suggest that DNA methods for HLA typing be developed for our black population. From the Department of General Surgery (T.P.T., M.C.M.M., A.K., S.N.) and Medical Research Council (P.B.), Medical University of Southern Africa, South Africa. Address reprint requests to Prof M.C.M. Modiba, Department of General Surgery, PO Box 231, MEDUNSA, 0204, South Africa.
© 2002 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/02/$–see front matter PII S0041-1345(02)03426-7
Transplantation Proceedings, 34, 2565–2566 (2002)
2565
2566
THULO, MODIBA, KOBRYN ET AL
Table 1. Causes of Graft Loss in Living Related Donation Rejection Hyperacute Acute Chronic Death with functioning allografts—septicemia Recurrent disease— oxalosis
1 1 7 4 1
REFERENCES 1. Barger BO, Hudson SL, Shroyer TW, et al: Clin Transpl 217, 1987 2. Koyama H, Cecka JM: Clin Transpl 269, 1991 3. Valente JF, Hariharan S, Peddi VR, et al: Clin Transpl 11:231, 1997
4. Gastron RS, Hudson SL, Deierhoi MH, et al: Transplantation 53:103, 1992 5. Van Buren DH, Richie RE, Nylander W, et al: South Med J 84:715, 1991 6. Raofi V, Holman DM, Coady N, et al: Am J Surg 177:29, 1999 7. Kerman RH, Kimball PM, Van Buren CT, et al: Transplantation 51:338, 1991 8. Butkus DE, Meydrech EF, Raju SS: N Eng J Med 327:840, 1992 9. Sehgal AR: Am J Kidney Dis 35:S148, 2000 10. Koyama H, Cecka JM, Terasaki PI: Transplantation 57: 1064, 1994 11. Cecka JM: Clin Transpl 363, 1995 12. Isaacs RB, Nock SL, Spencer CE, et al: Am J Kidney Dis 34:706, 1999 13. Modiba MCM, Mzamane DVA, Pantanowitz D, et al: Transplant Proc 21:2010, 1988 14. Modiba MCM, Ngcobo TK, Wolf JS, et al: S Afr J Surg 32:99, 1994