- Email: [email protected]
Transfusion therapy for renal transplant candidates
Transfusion Therapy for Renal Transplant Candidates HERBERT F. POLESKY, MD,* AND LARRY C. LASKY, MDf Improved graft survival was observed in cadaver-kidney recipients prepared with random donor blood transfusions and in selected living-related-kidney recipients primed with transfusions from the kidney donor. This seems to justify a purposeful transfusion policy in these patients. Human Pathol 14:275-277, 1983.
Selection of blood and components requires a careful evaluation of the specific needs of each patient and consideration of potential risks in comparison with the benefit expected from the transfusion. Although the usual indications for transfusions may be present in renal transplant candidates, these patients present a unique feature that should be considered in their management--this is the potentially beneficial effect of transfnsions on the acceptance and survival of the renal allograft. Prior to 1974, a great effort was made to limit the exposure of potential transplant recipients to any blood component containing HLA antigens. This transfusion strategy was based on observations suggesting that prior immunization to HLA was detrimental to graft survival) -3 In 1974, Opelz and Terasaki 4 reported that, contrary to what was expected, patients with muhiple transfusions prior to receipt of a cadaver renal allograft had better outcomes than did patients who received no t r a n s f u s i o n s or only f r o z e n - t h a w e d deglycerolized red cells (FTD-RBC). Both retrospective and prospective studies from numerous centers have confirmed that transfusions administered prior to transplantation have a beneficial effect on renal allograft survival (table I). Although the benefit of transfilsion has been established for recipients of grafts from cadavers and some from living related donors, many questions about purposeful transfusion therapy remain, including: 1) How much blood is needed? 2) When should the transfusions be given? 3) What component should be used? 4) Who should be selected as the donor? 5) Why does transfusion prolong graft survival? T h e a m o u n t o f blood required to produce a beneficial effect is critical, since each donor exposure increases the risk to the recipient. Thus, the detrimental effect of hepatitis (hepatitis virus types B and non-A, non-B), cytomegalovirus infection, and, most * Director, Minneapolis War Memorial Blood Bank, and Professor, Department of Lab Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota. t Associate Medical Director, Minneapolis War Memorial Blood Bank, and Instructor, Department of Lab Medicine and t'athology, University of Minnesota Medical School, Minneapolis, Minnesota . . . . . Address correspondence and requeststo Dr~ Polesky: Minneapolis War Memorial Blood Bank, 2304 Park Ave South, Minneapolis, MN 55404.
275
important, immunization must be considered. T h e incidence of lymphocytotoxic antibodies increases with the number of transfusions and pregnancies: These antibodies, which are found in about 40 per cent of patients given more than 11 transfusion, 6 can lessen the change of finding a compatible kidney and in some instances significantly prolong dialysis therapy prior to transplantation. Studies by Terasaki and coworkers 4"7 have suggested ttmt at least ten units are necessary to optimize the beneficial effects of transfusion. Others s'~ have reported that one unit is as effective as mulitple units and that more than five units are no more effective than are fewer than five. It is also unclear whether each transfusion should be equivalent to a standard unit of red cells (300 ml, hematocrit ~<80) or whether a smaller aliquot fi'om a donor would be equally effective, 1~ The timing of transfusion episodes has received considerable study. 9'11-13 If, as suggested iJy some, transfusion at the time of transplantation were as effective as transfusion weeks before surgery, then the problem of development ofcytotoxic antibodies could be eliminated. Although there may be some beneficial effect of transfusion on the day of transplantation, this is not the same effect and is n o t of the same magnitude as that of preoperative transfusion (table 2). T h e exact interval between transfusions and transplantation does not appear to be critical, and transfnsions given between six months and ten days prior to surgery are equally beneficial. It is possible that the effect from prior transfusion may last for many years. Certainly earlier transfilsions and pregnancies increase the chance that the patient will develop detectable cytotoxic antibodies. The selection of a specific component to achieve maximal benefit from pretransplantation transfusion should be dictated by knowledge of those factors in the transfusion that are responsible for the effect. These factors are currently unknown, although the effect is commonly attributed to white ceils. Experimental data in several animal models show that various transfusion protocols can prolong graft survival. ~4-~6At least one study suggests that small doses of leukocytes are more beneficial than large doses. 17 These observations may explain the different results obtained from the use of red cell preparations that lmve been modified to remove leukocytes. In our studies TM and in several others, ~9'2~FTD-RBCs were as effective as ordinary red cells or whole blood in prolongingsurvival of renal allografts. Although these leukocyte-poor c o m p o n e n t s are more costly, they pose less risk o f immunization to HLA antigens. Others have reported that, regarding graft survival, recipients of FTD-RBCs derive no benefit, or reduced benefit, from transfusion. 2t It is possible that
HUMAN PATHOLOGY
Volume t4, No. 3 (March t983}
TABLE 4. Effect of Transfusion on Renal AIlografl Survival
Reference Polesky et al. ts
Fuller et a l ) 9
Opelz et al. 7
F e d u s k a et al?
One-year G r a f t Survival (%)
Components Transfused N o u e (n = 17) N o n e (n = 16)
26 100
Comment Cadaver donor Living related d o n o r
M i x t u r e (n = 80) F T D - R B C (n = 31)
71 87
N o n e (n = 16) M i x t u r e (n = 48) F T D - R B C (n = 21)
25 76 76
N o n e (n - 304) Red cells (n = 256) W a s h e d r e d cells (n = 33) F T D - R B C (n = 21)
41 60 62 30
2 - 4 units
Red cells (n = 213) W a s h e d r e d cells (n = 33) F T D - R B C (n = 16)
68 52 55
5 - 1 0 units
N o n e (n = 178) M i x t u r e (n = 275) M i x t u r e (n = 149)
~30 ~59 ~59
Cadaver donor Intentional t r a n s f u s i o n (5 units)
1-5units > 5 units
ABBREVIATION: F T D - R B C = f r o z e n - t h a w e d degl)'cerolized r e d cells
TABLE 2. Time of Transfusion and Renal Allograft Survival
Reference Feduska et al?
Stiller et a l ) 2
Receipt of Transfusion None (n = 130) Day of transplantation (n = 48) Preoperative (n = 254) Pretransfusion and day of transplantation (n = 170) None (n = 32) Day of transplantation (n = 24)
studies in progress will show that huffy-coat concentrates effectively induce the beneficial effect o f transfusion. 22 Blood for preoperative transfusion of transplant recipients who are scheduled to receive a cadaver kidney should be from random unrelated donors who otberwisemeet established donor criteria. If a living related kidney donor is available, the transfusion of blood from random donors may also be beneficial.23 Recent studies indicate that blood or buffy coat from the prospective kidney donor (donor-specific transfusion, or DST) may be more beneficial,z4 In these related donor recipient pairs with a poor HLA match, DST results in graft survival rates similar to those achieved in transplantation between HLA-identical siblings. Howeyer, approximately 30 per cent of patients who receive DST develop a positive crossmatch (at 37~ T cell lymphocytotoxicity), which precludes use of the living related donor3 ~ Protocols utilizing immunosuppression with the DST or aging of the donor blood may help to reduce the incidence of antibodies to the donor. 26 The mechanism whereby transfusion exerts its beneficial effect on graft survival is unknown. A few hyper-responsive persons are selected from the pool of potential kidney recipients because they become 276
One-year Graft Survival (e/o) ~30 ~38 ~61 ~58 44 79
immnnized against all donors. In others, tile kidney that is found to be crossmatch-compatible is more highly selected because of the antibodies made by potential recipients following transfusionY It is possible that these are persons (about 10 per cent) who would reject their initial transplant and who have become "protected" by preoperative transfusion. Most of the beneficial effect of transfusion occurs during the first few months following transplantation. GThe percentage of first graft failure in patients given five or more transfusions is similar to the percentage in nontransfused patients if the graft survives and functions for at least three months. This suggests that the beneficial effect is due to avoidance of tile early rejection problems, possibly by "selecting out" the responders. The more likely explanation for the protective effect o f prior t r a n s f u s i o n is tbat a specific or nonspecific immunologic response to the donor blood occurs. Whether this response is formation of enhancing antibodies, alteration in suppressor T-cell activity, or reduction of immunologic responsiveness has not been established. Although many unresolved questions about tile beneficial effects of preoperative transfusion for potential renal allograft recipients remain, transfusion
TRANSFUSIONIN RENALTRANSPLANTATION(Polesky & Lasky]
of red cells containing small amounts o f white cells or white cell fragments reduces the rate of early rejection observed in nontransfused patients. Although this effect is additive to HLA-A,B and DR matching and to other factors, 6 the value of purposeful transfusion seems to outweigh the risks of transfusionindnced infection and immunization.
13. 14.
15.
REFERENCES
16.
1. Kissmeyer-Nielsen F, Olson S, Peterson V: Hyperacute rejection o f kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet 2:622, 1966. 2. vanHooffJP, van der Steen GJ, Scbippers HMA, et ah Efficacy of HL-A matching in Eurotransplant. Lancet 2:1385, 1972 3. Opelz G, Mickey MR, Terasaki PI: HL-A and kidney transplants: re-examination. Transplantation 17:371, 1974 4. Opelz G, Terasaki PI: Poor kidney transplant survival in recipients with frozen-blood transfusions or no transfusions. Lancet 2:696, 1974 5. Polesky HF: Leukocyte-poor blood: a study in the evolution of component therapy. In A Seminar on Blood Components: E Unum Pluribus. American Association of Blood Banks, 1977, p 53 6. Terasaki PI, Perdue S, Ayoub G, et al: Reduction of accelerated failures by transfusion. Transplant Proc 14:251, 1982 7. Opelz G, Terasaki PI: I n t e r n a t i o n a l s t u d y ot2. histocompatibility in renal transplantation. Transplantation 33:87, 1982 8. Sirchia G, Mercuriali F, Scalamogna M, et al: Evaluation of the blood transfusion of the North Italy transplant program. Transplantation 31:388, 1981 9. Feduska NJ, Amend wJ, Vincenti F, et ah Blood transfusions before and on the day of transplantation: effects on cadaver graft survival. Transplant Proc 14:302, 1982 10. Sirchia G, Mercuriali F, Pizzi C, et al: Blood transfusion and kidney transplantation: effect of small doses of blood on kidney graft function and survival. Transplant Proc 14:263, 1982 I 1. Williams KA, Ting A, French ME. et aI: Peroperative blood transfusions improve cadaveric renal-allograft survival in non-transfused recipients. Lancet 1:1104, 1980 12. Stiller CR, Sinclair NR, Sheppard RR, et ah Beneficial effect of
17. 18. 19. 20. 21. 22. 23. 24.
25.
26. 27.
277
operation-day blood transfusions on human renal-allograft survival. Lancet 1:169, 1978 Specs EK, Vaughn WK, Williams GM, et al: Effects of blood transfusion on cadaver renal transplantation. Transplantation 30:455, 1980 Abouna GM, Barabos AZ, Pazderka V, et al: The role of prior immunization with whole blood and with skin grafts on the survival of renal allografts in mongrel dogs. Transplant Proc 9:265, 1977 Heystek CA, vanLeersum RH, Balner H: Prolongation of baboon to rhesus kidney xenograft survival by pretransplant rhesus blood transfusions. Transplantation 25:165, 1978 Martin DC, ttewitt CW, Osborne JC, et al: Enhanced kidney graft survival in rats by single or multiple blood transfusion(s) and various blood products. Transplant Proc 14:407, 1982 Zimmerman C: Enhancing potential of whole blood. Transplant Proc 9:1081, 1977 Polesky HF, McCullough JJ, Yunis E, et al: The effects of transfusion of frozen-thawed deglycerolized red cells on renal graft survival. Transplantation 24:449, 1977 Fuller TC, Burroughs JC, Delmonico FL, et ah Influence of frozen blood transfusions on renal allograft survival. Transplant Proc 14:293, 1982 Briggs JD, Canavan JSF, Dick HM, et ah Influence of HLA matching and blood transfusion on renal allograft survival. Transplantation 25:80, 1978 Opelz G, Terasaki PI: I m p r o v e m e n r o f kidney-graft survival with increased numbers o f blood transfusions. N Engl J Med 299:799, 1978 Takahashi H, lwaki Y, Terasaki PI, et al: Deliberate buff)'coat transfusions and the risk of antibody formation. Transplant Proc 14:349, 1982 Opelz G, Mickey MR, Terasaki PI: Blood transfusions and kidney transplants: remaining controversies. Transplant Proc 13:136, 1981 Salvatierra O, Iwaki Y, Vincenti F, et al: Update on the University of California at San Francisco experience with donor-specific blood transfusions. Transplant Proc 14:353, 1982 Salvatierra O: Experience and future considerations with donor-specific blood transfusions in living-related transplantation. A m J Kidney Dis 1:119, 1981 LightJA, Metz S, Oddenino K, et al: Fresh versus stored blood in donor-specific transfusion. Transplant Proc 14:296, 1982 Perkins HA: HLA antigens and blood transfusions: effects on renal transplants. Transplant Proc 9(suppl 1):229, 1977
Selection of blood and components requires a careful evaluation of the specific needs of each patient and consideration of potential risks in comparison with the benefit expected from the transfusion. Although the usual indications for transfusions may be present in renal transplant candidates, these patients present a unique feature that should be considered in their management--this is the potentially beneficial effect of transfnsions on the acceptance and survival of the renal allograft. Prior to 1974, a great effort was made to limit the exposure of potential transplant recipients to any blood component containing HLA antigens. This transfusion strategy was based on observations suggesting that prior immunization to HLA was detrimental to graft survival) -3 In 1974, Opelz and Terasaki 4 reported that, contrary to what was expected, patients with muhiple transfusions prior to receipt of a cadaver renal allograft had better outcomes than did patients who received no t r a n s f u s i o n s or only f r o z e n - t h a w e d deglycerolized red cells (FTD-RBC). Both retrospective and prospective studies from numerous centers have confirmed that transfusions administered prior to transplantation have a beneficial effect on renal allograft survival (table I). Although the benefit of transfilsion has been established for recipients of grafts from cadavers and some from living related donors, many questions about purposeful transfusion therapy remain, including: 1) How much blood is needed? 2) When should the transfusions be given? 3) What component should be used? 4) Who should be selected as the donor? 5) Why does transfusion prolong graft survival? T h e a m o u n t o f blood required to produce a beneficial effect is critical, since each donor exposure increases the risk to the recipient. Thus, the detrimental effect of hepatitis (hepatitis virus types B and non-A, non-B), cytomegalovirus infection, and, most * Director, Minneapolis War Memorial Blood Bank, and Professor, Department of Lab Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota. t Associate Medical Director, Minneapolis War Memorial Blood Bank, and Instructor, Department of Lab Medicine and t'athology, University of Minnesota Medical School, Minneapolis, Minnesota . . . . . Address correspondence and requeststo Dr~ Polesky: Minneapolis War Memorial Blood Bank, 2304 Park Ave South, Minneapolis, MN 55404.
275
important, immunization must be considered. T h e incidence of lymphocytotoxic antibodies increases with the number of transfusions and pregnancies: These antibodies, which are found in about 40 per cent of patients given more than 11 transfusion, 6 can lessen the change of finding a compatible kidney and in some instances significantly prolong dialysis therapy prior to transplantation. Studies by Terasaki and coworkers 4"7 have suggested ttmt at least ten units are necessary to optimize the beneficial effects of transfusion. Others s'~ have reported that one unit is as effective as mulitple units and that more than five units are no more effective than are fewer than five. It is also unclear whether each transfusion should be equivalent to a standard unit of red cells (300 ml, hematocrit ~<80) or whether a smaller aliquot fi'om a donor would be equally effective, 1~ The timing of transfusion episodes has received considerable study. 9'11-13 If, as suggested iJy some, transfusion at the time of transplantation were as effective as transfusion weeks before surgery, then the problem of development ofcytotoxic antibodies could be eliminated. Although there may be some beneficial effect of transfusion on the day of transplantation, this is not the same effect and is n o t of the same magnitude as that of preoperative transfusion (table 2). T h e exact interval between transfusions and transplantation does not appear to be critical, and transfnsions given between six months and ten days prior to surgery are equally beneficial. It is possible that the effect from prior transfusion may last for many years. Certainly earlier transfilsions and pregnancies increase the chance that the patient will develop detectable cytotoxic antibodies. The selection of a specific component to achieve maximal benefit from pretransplantation transfusion should be dictated by knowledge of those factors in the transfusion that are responsible for the effect. These factors are currently unknown, although the effect is commonly attributed to white ceils. Experimental data in several animal models show that various transfusion protocols can prolong graft survival. ~4-~6At least one study suggests that small doses of leukocytes are more beneficial than large doses. 17 These observations may explain the different results obtained from the use of red cell preparations that lmve been modified to remove leukocytes. In our studies TM and in several others, ~9'2~FTD-RBCs were as effective as ordinary red cells or whole blood in prolongingsurvival of renal allografts. Although these leukocyte-poor c o m p o n e n t s are more costly, they pose less risk o f immunization to HLA antigens. Others have reported that, regarding graft survival, recipients of FTD-RBCs derive no benefit, or reduced benefit, from transfusion. 2t It is possible that
HUMAN PATHOLOGY
Volume t4, No. 3 (March t983}
TABLE 4. Effect of Transfusion on Renal AIlografl Survival
Reference Polesky et al. ts
Fuller et a l ) 9
Opelz et al. 7
F e d u s k a et al?
One-year G r a f t Survival (%)
Components Transfused N o u e (n = 17) N o n e (n = 16)
26 100
Comment Cadaver donor Living related d o n o r
M i x t u r e (n = 80) F T D - R B C (n = 31)
71 87
N o n e (n = 16) M i x t u r e (n = 48) F T D - R B C (n = 21)
25 76 76
N o n e (n - 304) Red cells (n = 256) W a s h e d r e d cells (n = 33) F T D - R B C (n = 21)
41 60 62 30
2 - 4 units
Red cells (n = 213) W a s h e d r e d cells (n = 33) F T D - R B C (n = 16)
68 52 55
5 - 1 0 units
N o n e (n = 178) M i x t u r e (n = 275) M i x t u r e (n = 149)
~30 ~59 ~59
Cadaver donor Intentional t r a n s f u s i o n (5 units)
1-5units > 5 units
ABBREVIATION: F T D - R B C = f r o z e n - t h a w e d degl)'cerolized r e d cells
TABLE 2. Time of Transfusion and Renal Allograft Survival
Reference Feduska et al?
Stiller et a l ) 2
Receipt of Transfusion None (n = 130) Day of transplantation (n = 48) Preoperative (n = 254) Pretransfusion and day of transplantation (n = 170) None (n = 32) Day of transplantation (n = 24)
studies in progress will show that huffy-coat concentrates effectively induce the beneficial effect o f transfusion. 22 Blood for preoperative transfusion of transplant recipients who are scheduled to receive a cadaver kidney should be from random unrelated donors who otberwisemeet established donor criteria. If a living related kidney donor is available, the transfusion of blood from random donors may also be beneficial.23 Recent studies indicate that blood or buffy coat from the prospective kidney donor (donor-specific transfusion, or DST) may be more beneficial,z4 In these related donor recipient pairs with a poor HLA match, DST results in graft survival rates similar to those achieved in transplantation between HLA-identical siblings. Howeyer, approximately 30 per cent of patients who receive DST develop a positive crossmatch (at 37~ T cell lymphocytotoxicity), which precludes use of the living related donor3 ~ Protocols utilizing immunosuppression with the DST or aging of the donor blood may help to reduce the incidence of antibodies to the donor. 26 The mechanism whereby transfusion exerts its beneficial effect on graft survival is unknown. A few hyper-responsive persons are selected from the pool of potential kidney recipients because they become 276
One-year Graft Survival (e/o) ~30 ~38 ~61 ~58 44 79
immnnized against all donors. In others, tile kidney that is found to be crossmatch-compatible is more highly selected because of the antibodies made by potential recipients following transfusionY It is possible that these are persons (about 10 per cent) who would reject their initial transplant and who have become "protected" by preoperative transfusion. Most of the beneficial effect of transfusion occurs during the first few months following transplantation. GThe percentage of first graft failure in patients given five or more transfusions is similar to the percentage in nontransfused patients if the graft survives and functions for at least three months. This suggests that the beneficial effect is due to avoidance of tile early rejection problems, possibly by "selecting out" the responders. The more likely explanation for the protective effect o f prior t r a n s f u s i o n is tbat a specific or nonspecific immunologic response to the donor blood occurs. Whether this response is formation of enhancing antibodies, alteration in suppressor T-cell activity, or reduction of immunologic responsiveness has not been established. Although many unresolved questions about tile beneficial effects of preoperative transfusion for potential renal allograft recipients remain, transfusion
TRANSFUSIONIN RENALTRANSPLANTATION(Polesky & Lasky]
of red cells containing small amounts o f white cells or white cell fragments reduces the rate of early rejection observed in nontransfused patients. Although this effect is additive to HLA-A,B and DR matching and to other factors, 6 the value of purposeful transfusion seems to outweigh the risks of transfusionindnced infection and immunization.
13. 14.
15.
REFERENCES
16.
1. Kissmeyer-Nielsen F, Olson S, Peterson V: Hyperacute rejection o f kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet 2:622, 1966. 2. vanHooffJP, van der Steen GJ, Scbippers HMA, et ah Efficacy of HL-A matching in Eurotransplant. Lancet 2:1385, 1972 3. Opelz G, Mickey MR, Terasaki PI: HL-A and kidney transplants: re-examination. Transplantation 17:371, 1974 4. Opelz G, Terasaki PI: Poor kidney transplant survival in recipients with frozen-blood transfusions or no transfusions. Lancet 2:696, 1974 5. Polesky HF: Leukocyte-poor blood: a study in the evolution of component therapy. In A Seminar on Blood Components: E Unum Pluribus. American Association of Blood Banks, 1977, p 53 6. Terasaki PI, Perdue S, Ayoub G, et al: Reduction of accelerated failures by transfusion. Transplant Proc 14:251, 1982 7. Opelz G, Terasaki PI: I n t e r n a t i o n a l s t u d y ot2. histocompatibility in renal transplantation. Transplantation 33:87, 1982 8. Sirchia G, Mercuriali F, Scalamogna M, et al: Evaluation of the blood transfusion of the North Italy transplant program. Transplantation 31:388, 1981 9. Feduska NJ, Amend wJ, Vincenti F, et ah Blood transfusions before and on the day of transplantation: effects on cadaver graft survival. Transplant Proc 14:302, 1982 10. Sirchia G, Mercuriali F, Pizzi C, et al: Blood transfusion and kidney transplantation: effect of small doses of blood on kidney graft function and survival. Transplant Proc 14:263, 1982 I 1. Williams KA, Ting A, French ME. et aI: Peroperative blood transfusions improve cadaveric renal-allograft survival in non-transfused recipients. Lancet 1:1104, 1980 12. Stiller CR, Sinclair NR, Sheppard RR, et ah Beneficial effect of
17. 18. 19. 20. 21. 22. 23. 24.
25.
26. 27.
277
operation-day blood transfusions on human renal-allograft survival. Lancet 1:169, 1978 Specs EK, Vaughn WK, Williams GM, et al: Effects of blood transfusion on cadaver renal transplantation. Transplantation 30:455, 1980 Abouna GM, Barabos AZ, Pazderka V, et al: The role of prior immunization with whole blood and with skin grafts on the survival of renal allografts in mongrel dogs. Transplant Proc 9:265, 1977 Heystek CA, vanLeersum RH, Balner H: Prolongation of baboon to rhesus kidney xenograft survival by pretransplant rhesus blood transfusions. Transplantation 25:165, 1978 Martin DC, ttewitt CW, Osborne JC, et al: Enhanced kidney graft survival in rats by single or multiple blood transfusion(s) and various blood products. Transplant Proc 14:407, 1982 Zimmerman C: Enhancing potential of whole blood. Transplant Proc 9:1081, 1977 Polesky HF, McCullough JJ, Yunis E, et al: The effects of transfusion of frozen-thawed deglycerolized red cells on renal graft survival. Transplantation 24:449, 1977 Fuller TC, Burroughs JC, Delmonico FL, et ah Influence of frozen blood transfusions on renal allograft survival. Transplant Proc 14:293, 1982 Briggs JD, Canavan JSF, Dick HM, et ah Influence of HLA matching and blood transfusion on renal allograft survival. Transplantation 25:80, 1978 Opelz G, Terasaki PI: I m p r o v e m e n r o f kidney-graft survival with increased numbers o f blood transfusions. N Engl J Med 299:799, 1978 Takahashi H, lwaki Y, Terasaki PI, et al: Deliberate buff)'coat transfusions and the risk of antibody formation. Transplant Proc 14:349, 1982 Opelz G, Mickey MR, Terasaki PI: Blood transfusions and kidney transplants: remaining controversies. Transplant Proc 13:136, 1981 Salvatierra O, Iwaki Y, Vincenti F, et al: Update on the University of California at San Francisco experience with donor-specific blood transfusions. Transplant Proc 14:353, 1982 Salvatierra O: Experience and future considerations with donor-specific blood transfusions in living-related transplantation. A m J Kidney Dis 1:119, 1981 LightJA, Metz S, Oddenino K, et al: Fresh versus stored blood in donor-specific transfusion. Transplant Proc 14:296, 1982 Perkins HA: HLA antigens and blood transfusions: effects on renal transplants. Transplant Proc 9(suppl 1):229, 1977