Studies on eleven kidney transplants from non-heart-beating donors.

This study was performed to analyze postoperative courses and complications, retrospectively, following transplants from non-heart-beating donors and to examine the correlation between early graft function and clinical parameters. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. Warm ischemic time was less than 30 min in all cases, and total ischemic time ranged from 8.4 hours to 27.9 hours. Rejection reactions occurred in seven cases, two of which were vascular rejections. Infectious disease complications included CMV in two cases, interstitial pneumonia in one case and fungal infection in one case. One patient died from interstitial pneumonia, and three patients had to be restarted on dialysis due to loss of function of the grafted kidney. The remaining seven patients all made full recoveries. All of the 16 patients who underwent living related kidney transplantations during the same period made full recoveries. Both the donor's gender and the latest creatinine level of the donor influenced the posttransplant dialysis period. The posttransplant dialysis period significantly influenced the creatinine level one month after transplant. These results suggest that patients who undergo kidney transplants from non-heart-beating donors have higher rates of complications than patients who undergo living related kidney transplantation. It is important that, in cases where the donor's creatinine level is high, especially when the donor is male, the kidney is carefully retrieved and transported to the recipent hospital to shorten the ischemic period as much as possible.

Allochronic overlapping malignancies after renal transplantation in a patient with p53 gene mutation: report of a case.

We report a rare case of the development of various tumors over a 16-year period after renal transplantation. A 56-year-old woman underwent renal transplantation using a US kidney. Immunosuppressive treatment consisted of a triple regimen of methylprednisolone, azathioprine, and mizoribine. Left breast cancer was diagnosed 9 years after the renal transplantation, then colon cancers and meningeal epidermal meningioma were diagnosed, 10 years and 12 years post-transplant, respectively. During the investigations for the breast and colon cancers, a p53 gene mutation was detected. A deterioration of renal function was found 16 years after the transplant and graft biopsy confirmed chronic rejection. We suggest that the effects of the immunosuppressive drugs combined with the p53 gene abnormality accelerated tumor development in this patient.

Downregulation of interleukin-12p35 and upregulation of interleukin-12p40 mRNA expression in heart allografts by blood transfusion from granulocyte colony-stimulating factor-treated donors.

Pretransplant treatment of recipients with recombinant human granulocyte colony-stimulating factor (rhG-CSF, 250 microg/kg/day s.c. for 5 days) facilitates heart allograft acceptance in tacrolimus-treated rat recipients. We examined effectiveness of transfusion of in vivo rhG-CSF-treated blood since rhG-CSF induces immunoregulatory cells in human blood. DA heart grafts were transplanted into tacrolimus (2 mg/kg i.m. on day 0)-treated Lewis recipients. Although graft survival prolongation by blood transfusion on day 0 from rhG-CSF-treated syngeneic Lewis was comparable to that in directly rhG-CSF-pretreated recipients (p = 0.22), transfusion of rhG-CSF-treated allogeneic DA blood was much more effective (p = 0.0016). Intragraft cytokine mRNA levels were measured by reverse transcription and real-time polymerase chain reaction at 24 h after transplantation. IL-12p35 expression was downregulated by both treatments. Notably, IL-12p40 was upregulated by rhG-CSF-treated DA blood transfusion but downregulated by transfusion of rhG-CSF-treated isogeneic blood. Differential expression of IL-12 subunits was associated with facilitation of graft acceptance by rhG-CSF-treated donor blood transfusion.

Facilitation of tacrolimus-induced heart-allograft acceptability by pretransplant host treatment with granulocyte colony-stimulating factor: interleukin-12-restricted suppression of intragraft monokine mRNA expression.

BACKGROUND: Because recombinant human granulocyte colony-stimulating factor (rhG-CSF) is known to modulate function of antigen-presenting cells, we examined effects of pretransplant host treatment with rhG-CSF on allograft survival. METHODS: In DA-to-Lewis rat heart transplantation, hosts were given pretransplant injections of rhG-CSF (250 microg/kg/day subcutaneously from day -5-0) and/or posttransplant injections of tacrolimus (2 mg/kg/day intramuscularly from day 0-3). Cytokine mRNA levels in grafts were measured by real-time reverse-transcription polymerase chain reaction. RESULTS: rhG-CSF pretreatment was effective in prolonging allograft survival only in tacrolimus-treated hosts (P <0.001). Intragraft mRNA expression of interleukin (IL)-12 subunits (p35, p40) at 24 hours after transplantation was significantly (P <0.05) down-regulated by the addition of rhG-CSF and was associated with suppression of interferon-gamma levels on day 6, although other proinflammatory cytokines (tumor necrosis factor -alpha, IL-1beta, IL-6, IL-18) and anti-inflammatory cytokines (IL-10, transforming growth factor-beta) were not. CONCLUSIONS: rhG-CSF pretreatment down-regulates intragraft expression of the type-1 T-helper cell (Th1)-driving cytokine IL-12 and facilitates tacrolimus-induced graft acceptance.

Upregulation of intragraft interleukin-10 by infusion of granulocyte colony-stimulating factor-mobilized donor leukocytes.

We examined the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized donor leukocyte infusion (G-DLI) on facilitation of allograft survival using heart transplantation from DA to Lewis rats that were transiently treated with tacrolimus (2 mg/kg i.m. on day 0). Other DA rats were given G-CSF (250 microg/kg/day s.c. from days -5 to 0), and isolated leukocytes were infused into Lewis recipients after surgery. Cytokine mRNA levels were quantified by reverse transcription and real-time polymerase chain reaction. After G-CSF treatment, leukocytes in circulation increased by 7.6 times and secreted in-vitro 6.0-times-higher levels of IL-10 after lipopolysaccharide stimulation than did untreated leukocytes. G-DLI facilitated graft survival dose-dependently. Significant IL-10 mRNA upregulation was detected in grafts 24 h after surgery but not in the recipient's heart, spleen, or liver. On day 6, IFN-gamma and IL-2 mRNA levels were approximately half those of the control levels. Allograft-restricted IL-10 upregulation followed by type-1 cytokine downregulation can be achieved by the use of G-DLI.

Downregulation of both interleukin-12 and interleukin-2 in heart allografts by pretransplant host treatment with granulocyte colony-stimulating factor and tacrolimus.

Since recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been reported to induce immune deviation, we examined the effects of pretransplant treatment of recipients with rhG-CSF on heart allograft survival. Before heterotopic heart transplantation from DA to Lewis rats, recipients were given rhG-CSF (125microg/kg s.c. twice a day from day -5 to 0) and/or tacrolimus (2mg/kg i.m. on day 0). Combined treatment with both rhG-CSF and tacrolimus prolonged graft survival significantly (P<0.05), while rhG-CSF or tacrolimus alone did not. At 24h after transplantation, cytokine mRNA levels in the grafts were measured by reverse transcription and real-time polymerase chain reaction. IL-12 p35 expression was highly inhibited by rhG-CSF treatment, but tacrolimus did not change the levels. Conversely, rhG-CSF treatment did not affect IL-2 levels, while tacrolimus completely blocked its expression. Combined pretreatment was effective for suppressing acute rejection reaction by downregulating these two key type-1 cytokines, IL-12 and IL-2, with unchanged levels of IL-10.