Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation.
Early acute rejection episodes have a considerable influence on long-term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p < 0.05). 89% of the patients in the group being studied showed normal renal function after 1 yr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL-1 beta, IL-2, sIL-2R and IFN-gamma) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long-term allograft survival.
Fricke
L
L
Department of Internal Medicine, University of Lübeck School of Medicine, Germany.
Klüter
H
H
Feddersen
A
A
Doehn
C
C
Steinhoff
J
J
Hoyer
J
J
Sack
K
K
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011300:Preoperative Care; D011446:Prospective Studies
D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008775:Methylprednisolone