Open AccessBone marrow augmentation in kidney transplantation: a large animal study
Author(s) -
Gruessner R.W.G.,
Zhang K.Y.,
Dunning M.,
Nakhleh R.E.,
Gruessner A.C.
Publication year - 2001
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2001.tb00035.x
Subject(s) - tacrolimus , medicine , immunosuppression , bone marrow , kidney , globulin , miniature swine , transplantation , group a , gastroenterology , graft versus host disease , immunology
Specific immunomodulatory strategies are required to eliminate the need for lifelong dependence on debilitating immunosuppressants. One proposed strategy is to simultaneously transplant the kidney and infuse donor‐specific bone marrow cells. We prospectively studied the effect of unmodified donor‐specific bone marrow infusion (DSBMI) on rejection, infection, graft‐versus‐host disease (GvHD), and graft survival. We performed 57 kidney transplants in mixed lymphocyte culture (MLC)‐reactive, outbred pigs. The groups of recipient pigs differed according to the use of (1) indefinite versus short‐term tacrolimus‐based immunosuppression, (2) DSBMI, and (3) recipient preconditioning (RPC: whole body irradiation with 400 rads on day 0 and horse anti‐pig thymocyte globulin (ATG) on days ‐2, ‐1, and 0). In all, we studied eight groups: group 1, nonimmunosuppressed control pigs ( n = 8); group 2, nonimmunosuppressed DSBMI pigs ( n = 7); group 3, nonimmunosuppressed RPC + DSBMI pigs ( n = 5); group 4, tacrolimus (indefinite) pigs ( n = 11); group 5, tacrolimus (10 days only) pigs ( n = 5); group 6, DSBMI + tacrolimus (indefinite) pigs ( n = 8); group 7, DSBMI + tacrolimus (10 days only) pigs ( n = 6); and group 8, RPC + DSBMI + tacrolimus (indefinite) pigs ( n = 7). DSBMI alone (group 2) or in combination with RPC (group 3) did not prolong graft survival, as compared with nonimmunosuppressed controls (group 1). In groups 1, 2, and 3, all but one pig died from rejection; in group 3 only, 45% of the pigs died from concurrent infection or GvHD, indicating that RPC in combination with DSBMI aggravated the risk of generalized infection and GvHD. Post‐transplant immunosuppression ‐ irrespective of indefinite or short‐term administration ‐ was required for prolonged graft survival. With indefinite use of immunosuppression, graft survival rates and death rates from rejection were not different for pigs with (group 6) versus without (group 4) DSBMI; however, the death rate from infection was higher in group 6, suggesting that the bone marrow inoculum increased the risk of systemic infection. With short‐term use of immunosuppression, graft survival rates were higher and death rates from rejection lower for pigs with (group 7) versus without (group 5) DSBMI. But DSBMI and short‐term immunosuppression (group 7) failed to prolong survival beyond that achieved with indefinite immunosuppression (groups 4 and 6). Although the combination of DSBMI and short‐term immunosuppression (group 7) reduced the risk of infection, it did not avert severe rejection. The addition of RPC to DSBMI and indefinite immunosupsuppression clearly increased the risks of death from rejection, infection, GvHD, or a combination thereof. The optimal way to perform bone marrow augmentation after kidney transplantation remains to be determined.