Effects of cyclosporine, azathioprine, and steroids on the renal transplant, on the cytologic patterns of intragraft inflammation, and on concomitant rejection-associated changes in recipient blood.
We have investigated the impact of various immunosuppressive drugs and their combinations on the graft, on the intragraft inflammatory patterns of rejection, and on rejection-associated effects in the recipient circulation by fine-needle aspiration biopsy and an extensive computer program. The patients were randomized into three treatment groups, 32 patients each, with the following postoperative immunosuppression: (1) Aza (2.1 mg/kg/d) plus MP (3.6 mg/kg/d tapered to 0.5 mg/kg/d by day 15), (2) CsA (10 mg/kg/d tapered to 8 mg/kd/d by day 28) and, (3) CsA (as above) plus MP (3.6 mg/kg/d tapered to 0 mg/kg/d by day 9). The groups were homogeneous in regard to all tested pretransplantation parameters. Graft parenchymal cell morphology was significantly (P less than .05) deteriorated and urine output reduced in CsA-treated patients, compared to those receiving Aza + MP; concomitant administration of steroids partially (P = NS) protected against the CsA-associated effects. The first episode of inflammation occurred significantly earlier (P less than .001) in patients receiving initially only CsA, compared to those receiving Aza + MP or CsA + MP, the total duration of intragraft inflammation was longer and the clinical signs of rejection were significantly prolonged (.001 less than P less than .05). Although the influx of lymphocytes and monocytes into the graft and the peak intensity of intragraft inflammation was similar in the three groups of patients, the inflammatory patterns of rejection were distinctly different. The number of (T) lymphoblasts in CsA-treated grafts was significantly (P less than .05) lower and their appearance delayed, compared to those treated with Aza + MP and even lower and more delayed in grafts treated initially with CsA + MP. The number of (B) plasmablasts was also reduced and their appearance delayed, but the differences to conventional treatment with Aza + MP were smaller and no longer significant. On the other hand, a significant (P less than .01) early maturation of blood-borne monocytes into tissue macrophages was observed in the CsA-treated grafts in context of first rejection, which was lacking from those treated with CsA + MP or Aza + MP. In the blood, the first episodes of inflammation under CsA were associated with significant (P less than .001) thrombocytosis, which was lacking from the Aza + MP- and CsA + MP-treated patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Häyry
P
P
Department of Surgery, University of Helsinki, Finland.
von Willebrand
E
E
Ahonen
J
J
Eklund
B
B
Salmela
K
K
Höckerstedt
K
K
Pettersson
E
E
Koskimies
S
S
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use*; D006084:Graft Rejection; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000473:pathology; D016030:Kidney Transplantation; D013256:Steroids / Q000627:therapeutic use*; D013997:Time Factors
D003524:Cyclosporins; D013256:Steroids; D001379:Azathioprine