LOCAL TREATMENT OF RENAL ALLOGRAFTS, A PROMISING WAY TO REDUCE THE DOSAGE OF IMMUNOSUPPRESSIVE DRUGS

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Abstract
A method is described for continuous administration of immunosuppressive drugs directly into rat renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days. It is demonstrated that the technique as such has no detrimental or enhancing effects on renal allograft survival. Depending upon the pharmacokinetic properties of the drug administered, this technique allows a more or less selective treatment of renal allograft rejection. The method was used to test the effect of intrarenal administration of prednisolone on renal allograft survival. Intrarenal administration of this drug appeared to be superior to any other way of administration tested. A low dose of 4 mg/kg body weight per day given by continuous intrarenal infusion results in significant prolongation of graft survival, whereas continuous systemic administration of this dose is not effective. To induce prolongation of graft survival by i.p. administration the prednisolone dose had at least to be doubled. The results prove that during graft rejection local events within the graft are vulnerable to prednisolone. It is concluded that local treatment of allograft rejection is possible and that this approach represents a potentially important way to manipulate the immune response.