Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review.

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Lymphocyte subsets and Langerhans cells in sun-protected and sun-exposed skin of immunosuppressed renal allograft recipients.

BACKGROUND: Patients who have received renal allografts experience early aging of the skin, opportunistic infections, and an increased incidence of skin cancer. OBJECTIVE: We compared the density of lymphocyte subsets and Langerhans cells in normal-appearing skin of renal allograft recipients without skin cancer at 5 to 6 years (group 1) and 14 years after transplant (group 2) with a matched normal control group. METHODS: Biopsy specimens of sun-protected and exposed areas from 18 white, kidney allograft recipients (10 in group 1 and 8 in group 2) with normal renal function and from 10 healthy volunteers were semiquantitatively analyzed for dermal lymphocyte subsets and Langerhans cells. RESULTS: There was a statistically significant decrease in all dermal cell elements in the sun-protected skin of both groups of patients who had received grafts. The sun-exposed skin of group 2 also showed a significant decrease of dermal CD4+ and CD8+ lymphocytes, and group 1 had a significant decrease in dermal CD8+ lymphocytes. The dermal CD1a+ cell population in the sun-exposed skin from both grafted groups did not differ from the control group. CONCLUSION: Kidney transplant recipients showed dermal depletion of cells related to immune surveillance against tumors even before skin cancer occurred, and this depletion seemed to become more marked with the duration of immunosuppression.

Endolymphatic irradiation in preparation for renal transplantation: a 26-year's follow-up.

OBJECTIVE: The aim of the present study was to analyze the long-term evolution of patients submitted to endolymphatic irradiation as a pre-transplant preparation. SETTING: Referral center of university hospital. DESIGN: Case-control study. MAIN OUTCOMES MEASURES: The study was designed to evaluate the incidence of rejection, kidney loss, leukopenia, infection, and graft survival in the group treated (group 1) prior to surgery, compared to a control group (group 2) composed of patients under identical clinical conditions (sex, age, type of donor, immunosuppressive therapy and time of transplant) that did not undergo treatment preparation. PATIENTS: Patients were selected from amongst transplantation candidates on a long-term waiting list, some with a high level of antibodies against panel. The control group was chosen from amongst recently transplanted patients. Patients in the treated group received lipoiodine containing 131I with specific activity ranging between 4 and 6 mCu/ml. RESULTS: A significant difference between the two groups was found with regard to the incidence of rejection crises (21.0% in group 1 and 73.6% in group 2; P = 0.003), and the maintenance dose of azathioprine (smaller in group 1; P < 0.01). As to kidney graft loss due to rejection, a tendency to significance could be identified (10.5% in group 1 and 42.1% in group 2; P = 0.063); however, the difference was not significant between the two groups in terms of reversibility of rejection episodes during the first 60 post-transplant days. CONCLUSIONS: The authors concluded that this method, besides being relatively innocuous (there was no compromising of either the thyroid gland or of gonad function and there was no increase in tumor incidence), has an extended immunosuppressive effect, and can be indicated for cadaveric renal allograft recipients, especially those showing high panel reactivity.

Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P < 0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

Stored blood - an effective immunosuppressive method from unrelated donors: an 11-year follow-up

Thirty-seven patients were submitted to kidney trasnplantation after transfusion at 2-weeck intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of penel reactive antibodies (PRA) reative antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P<0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56 percent and 77 percent, respectively, for the treated group and 39,8 percent and 57.5 percent for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that tranfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process with-out impairing the adequate funsctioning of the renal graft.

[Cyclosporin A: experience of the Renal Transplant Unit of the Clinical Hospital of the Medical College of the University of Sao Paulo]. / Ciclosporina A: experiência da Unidade de Transplante Renal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.

The authors report their experience using cyclosporine-A (CsA) in renal transplant patients. When compared with azathioprine/prednisone, CsA contributed significantly to a better graft and patient survival, either if used associated with prednisone of with azathioprine plus prednisone. CsA was also used in substitution to azathioprine in patients with hepatopathy attributed to azathioprine toxicity. The initial results are promising. The association of CsA and azathioprine with corticosteroids withdrawal was used as an attempt to allow normal growth in children. This seems to be the best choice of treatment for children. Careful monitoring of CsA blood levels avoids, or at least, minimizes nephrotoxicity. To achieve therapeutic CsA levels, patients with liver damage need lower, while children need higher oral CsA doses. To summarise: when CsA in carefully used, it is an excellent immunosuppressive drug.

Lymphocytotoxic donor-specific response to fresh and stored blood. An experiment in immunosuppressed rhesus monkies (brief communication).

Transfusion of stored blood has been found to decrease the rate of antibody formation. Antigen immunogenicity and the recipient's immunoresponsiveness have a major role in the fate of the allograft. The combined effect of low immunogenicity and depressed responsiveness has been studied.

Irradiacao endolinfatica. Metodo util para imunessupressao em transplante renal. / Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

Foi analisado tardiamente a evolucao clinica e o destino do enxerto renal em 24 pacientes (grupo I) que receberam injecao endolinfatica do 131I como medida imunessupressora pre-transplante. O grupo-controle (grupo II) constituiu-se de 24 pacientes nao irradiados e comparaveis ao grupo I quanto a idade, sexo, diagnostico de doenca primaria, tipo de doador e terapia imunessupressora. Diferenca significativa entre os dois grupos foi encontrada com relacao a incidencia e reversibilidade das crises de rejeicao nos primeiros 60 dias pos-transplantes; perda de rim em rejeicao e dose de manutencao de azatioprina. Os autores concluem que o metodo, alem de inocuo, tem acao imunessupressora prolongada, podendo ser indicado para receptores de rim de cadaver, sobretudo os casos que apresentam a cross-match positivo contra antigenos HLA para painel

Immunosuppressive effect of intra-lymphatic irradiation.

The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation.