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.