Effects of photochemical donor pretreatment on the pattern of dog renal allograft infiltrating cells.

Kidneys were removed ten minutes after treating the donor with 1 mg of 8-methoxypsoralen per 1 kg b.w., during hypothermic preservation UVA-irradiated (intensity: 1.34 mJ/s) for 4 h and thereafter transplanted into ASDI dogs (n = 10). Fine needle aspiration biopsies were performed to analyze the inflammatory response. In comparison with untreated ASDI dogs (n = 9) PUVA pretreated renal grafts showed three important differences: 1. At the peak of the rejection process in the control group (day 8) the cellular infiltrate in the PUVA-pretreated kidneys was significantly diminished. 2. This reduction was caused by a significantly lower influx of monocytes/macrophages. 3. The peak of the cellular response in the PUVA group was delayed. These findings support the concept of reduced graft immunogenicity by pretransplant PUVA treatment.

[PUVA treatment of organ transplants--experimental and clinical results]. / PUVA-Behandlung von Organtransplantaten--experimentelle und klinische Ergebnisse.

The aim of the present study was to evaluate the influence of a pretreatment of the heart and kidney donor with the photosensitizer 8-methoxypsoralen plus ex vivo longwave ultraviolet irradiation of the graft (PUVA) on survival time and immunogenicity of rat heart and kidney allografts. PUVA pretreatment significantly prolonged the survival of these transplants in allogenic recipients. Furthermore, a synergistic effect with conventional immunosuppression (azathioprine, cyclosporine) was demonstrated. Immunohistological studies using monoclonal antibodies showed a significant reduction of MHC class II antigen expression in heart cryostat sections after PUVA treatment. In clinical kidney transplantation the number of rejection episodes was significantly lower in the first 3 months in the PUVA-treated patient group.

[Extending the survival time of allogenic heart and kidney transplants in the rat by a combination of PUVA transplant conditioning and cyclosporin treatment of the recipient]. / Verlängerung der Uberlebenszeit allogener Herz- und Nierentransplantate bei der Ratte durch eine Kombination von PUVA-Transplantatkonditionierung und Cyclosporin-Empfängerbehandlung.

Dose-response studies of cyclosporin (CsA) established that a dose of 2 mg kg body weight on day 0 was of therapeutic suboptimal value in rat kidney allotransplantation. When PUVA-treated heart and kidney allografts were transplanted into temporary CsA immunosuppressed recipients the graft survival rates were further improved as compared with PUVA alone. Forty vs. 18% (heart) and 70 vs. 40% (kidney) of the PUVA + CsA vs. PUVA treated allografts survived permanently. Therefore a synergistic effect of PUVA pretreatment and low-dose CsA therapy on rat heart and renal allograft survival was demonstrated.

[Comparison of inulin and creatinine clearance determinations in anesthesized and conscious rats]. / Vergleich von Inulin- und Kreatininclearancebestimmungen bei narkotisierten und wachen Ratten.

Two investigation methods of the renal function by means of the inulin and the endogenous creatinine clearance in narcotized and conscious rats are described in detail. The inulin clearance was 0.84 +/- 0.16 ml/min/100 g BW. The results of the creatinine clearance obtained by 6 various methods are widely different due to co-determination of foreign chromogens. Therefore, it is important to compare these results with the results of other analytical methods determining only the "true" creatinine.

Photochemical donor pretreatment in clinical kidney transplantation--preliminary report.

Extended experimental experience with the efficacy of pretreating the kidney donor and the allograft by means of photochemotherapy (photosensitizer + UVA irradiation = PUVA) was adopted in clinical kidney transplantation. In a preliminary unrandomized study similar patient populations were treated by generally uniform methods. Thirty-three PUVA-pretreated kidneys (group A) were compared with the experience regarding 26 non-pretreated kidney allografts (group B). The number of rejection episodes was significantly lower in the first 3 months in group A (p less than 0.05 vs group B) and fewer grafts failed because of irreversible rejection (2 vs 5). Furthermore, in group A the rate of infectious complications was lower (18% vs 34%). The cumulative allograft survival at 3 months was improved from 65% in group B to 81% in group A and at 12 months from 65% 76%, respectively. These differences were not significant. Therefore, our preliminary clinical experience with a photochemical donor pretreatment is encouraging and further use in a randomized study seems to be necessary.

Synergistic effect of photochemical donor pretreatment and cyclosporin therapy of the recipient on rat renal allograft survival.

Dose-response studies of cyclosporin (CsA) established that doses of 2 mg/kg body weight on 4 consecutive days (0-3) or higher gave complete suppression of rejection and permanent survival of all rat kidney allografts, while a dose of 2 mg/kg body weight on day 0 was much less effective in preventing deleterious rejection (30% permanent survival). Photochemical pretreatment of the kidney donor with 8-methoxypsoralen (8-MOP) and direct long-wave ultraviolet irradiation (UVA) of the kidney (PUVA) therapy) significantly prolonged the subsequent graft survival in allogeneic recipients. Forty per cent of the animals survived more than 100 days. However, when PUVA-treated kidney allografts were transplanted into temporary CsA immunosuppressed recipients (2 mg/kg on day 0) the graft survival rate was further improved. Seventy per cent of the PUVA + CsA-treated recipients survived permanently. Therefore, a synergistic effect of PUVA pretreatment and low-dose CsA therapy on rat renal allograft survival was demonstrated. The results suggested a possible clinical application of this treatment regimen in order to avoid high nephrotoxic CsA doses.