Long-term benefits and risks of cyclosporin A (sandimmun)--an analysis at 10 years.
To evaluate long-term benefits and risks of CyA therapy in renal transplantation, we analyzed the 10-year experience with all 59 patients who had received a first cadaveric renal graft until August 1983 and were immunosuppressed with CyA. We compared their actual graft survival with that of all 213 patients who had received a first cadaveric graft from 1967 until August 1983, but were immunosuppressed initially with azathioprine and prednisone (AzaP). For comparison of p-creatinine, proteinuria, blood pressure, lipids, uric acid and skin malignancies we evaluated the patients staying unchanged on initial therapy for 10 years (CyA = 12, AzaP = 53). RESULTS. (1) Actual graft survival at 10 years was 34% (20/59) with CyA and 27% (58/213) in AzaP treated patients (intention to treat) (P = .09 = ns). At 1 to 5 years, graft survival was 15% superior with CyA, but after 7 years the survival curve of the CyA-group has closely joined the chronic decline seen in the AzaP group. This behaviour could neither be explained by chronic CyA-nephrotoxicity nor by chronic rejection after switching from CyA to AzaP. (2) P-creatinine at 10 years was significantly (P < .03), but mildly elevated under CyA (130 +/- 52; AzaP = 109 +/- 65). (3) Proteinuria (g/d) at 10 years was not significantly different (CyA = 0.41 +/- 0.58, versus AzaP = 0.83 +/- 1.61). (4) Systolic blood pressure was higher at 10 years under CyA (152 +/- 19) than under AzaP (136 +/-) (P < .02), but diastolic pressure was not (89 +/- 10 versus 84 +/- 12; ns). Antihypertensive drug/patient was twice as high under CyA (1.25 versus 0.64 P < .02). (5) Cholesterol, triglyceride, HDL were not different. 75% of the CyA-patients were steroid free at 10 years, none of the AzaP-patients. (6) P-uric acid was not significantly different in both groups (494 +/- 192 vs 400 +/- 124), but 42% of CyA-patients were on uric acid lowering drug (given after at least one gout attack) as compared to 9% under AzaP (P < .006). (7) Seventeen percent of patients under CyA for 10 years had at least one skin cancer, not different from 15% of AzaP-patients. CONCLUSIONS. The main benefit of CyA was the better graft survival up to 5 years and the chance to stay free of steroids. The main risks of CyA were nephrotoxicity, hypertension and symptomatic hyperuricemia. No difference was found for hyperlipidemia and skin-malignancies.
Thiel
G
G
Department of Medicine, Kantonsspital Basel, University of Basel, Switzerland.
Bock
A
A
Spöndlin
M
M
Brunner
F P
FP
Mihatsch
M
M
Rufli
T
T
Landmann
J
J
D000959:Antihypertensive Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001794:Blood Pressure; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D011241:Prednisone / Q000627:therapeutic use; D011507:Proteinuria; D012307:Risk Factors; D013997:Time Factors
D000959:Antihypertensive Agents; D016572:Cyclosporine; D003404:Creatinine; D001379:Azathioprine; D011241:Prednisone