| Abstrakt: |
The use of cyclosporine as an immunosuppressive agent has improved graft survival after transplantation. However, the nephrotoxicity of cyclosporine is a serious clinical problem. After treatment with cyclosporine and prednisolone during the 1st year after renal transplantation, 106 patients were consecutively randomized to either treatment with azathioprine and prednisolone (Group Az) or cyclosporine and prednisolone (Group Cy) in a prospective controlled study during the following 1 yr. 51‐Cr‐EDTA clearance (CEDTA), blood pressure (BP), plasma concentrations of atrial natriuretic peptide (ANP), angiotensin II (Ang II), and aldosterone (Aldo), and urinary excretion rate of prostaglandin E2(PGE2) were determined at the start of the study and every 6 months. Systematic, blind and semiquantitative histopathologic analyses were performed on biopsies from the renal grafts at the start of the study and after 12 months. Comparison within groups showed that GFR increased in Group Az (44 to 48 ml/min, p < 0.05) and decreased in Group Cy (43 to 39 ml/min, p < 0.05) after 6 months, and that GFR was unchanged after 12 months in Group Az (42 ml/min) and reduced in Group Cy (39 ml/min, p < 0.05) compared to baseline level. Comparison between groups showed a significantly higher GFR in Group Az than in Group Cy after 6 months, but no significant difference in GFR at the start of the study or after 12 months. The extent of arteriolar hyalinosis increased significantly in Group Cy (0.82 to 1.72 score, p < 0.001) after 12 months but was unchanged in Group Az (0.97 to 0.94 score), whereas interstitial fibrosis increased to the same level in both groups. After 12 months, BP was decreased and ANP, PGE2, Ang II and Aldo were unchanged in Group Az. Contrariwise, in Group Cy BP remained unchanged, ANP and PGE2were increased, and Ang II and Aldo suppressed. The increased arteriolar hyalinosis during cyclosporine treatment most probably results in a higher BP than during azathioprine treatment. The higher ANP and PGE2during cyclosporine treatment may be compensatory phenomena in order to preserve graft function and reduce BP. Conversion to azathioprine treatment may be superior to continued cyclosporine treatment at least from 12 to 24 months after renal transplantation. |
