85963
document
Long-term consequences of different immunosuppressive regimens for renal allografts . The long-term effects of four different immunosuppressive regimens on renal allografts have been investigated up to four years . A total of 128 recipients of first cadaveric renal allograft were randomized , after an initial induction period , to receive either triple drug therapy -- i.e. , ( low-dose ) cyclosporine , azathioprine , and methylprednisolone , or any possible combination of two drugs -- i.e. , Aza plus CsA , Aza plus MP , and CsA plus MP . The actual four-year graft survival rates for the triple therapy , Aza plus CsA , Aza plus MP , and CsA plus MP groups were 72 % , 69 % , 75 % , and 59 % , and patient survival rates were 78 % , 81 % , 81 % , and 84 % , respectively , with no significant differences . The cumulative number of chronic rejections up to 4 years was 0.09 , 0.29 , 0.25 , and 0.34 per patient per group ( P = ns ) , respectively . At 2 , 3 , and 4 years posttransplantation , the graft function was significantly worse in the Aza plus MP group compared with the triple therapy group ( P < .05 ) . Of the 98 patients who did not have type I or II diabetes at the time of transplantation , 17 developed posttransplantation diabetes mellitus or an abnormal glucose tolerance test within 2 years posttransplantation . All these patients had received steroids and none of the patients without steroids had these abnormalities . At two years the mean cholesterol level was highest in the Aza plus MP group , 6.8 mmol/L and lowest in the group receiving triple therapy , 5.8 mmol/L ( P = ns ) . The use of ( low-dose ) CsA was not associated with lipid abnormalities or with disturbances in glucose metabolism . A protocol graft biopsy was performed at two years on all functioning kidneys , and the histological changes were scored blindly . No CsA-specific changes , except isometric vacuolation in tubuli , were found . Histological alterations characteristic of chronic rejection were expressed as " chronic allograft damage index . " Chronic allograft damage index was lowest in the triple therapy group , 1.5 , compared with the other groups , 3.2-4.3 ( P = .01 ) , indicating the least histopathological change in the triple therapy group . In conclusion , this long-term study did not show any serious cyclosporine-related side-effects when used in low dose in combination with two other drugs . Some side-effects , such as posttransplant diabetes mellitus and probably some lipid abnormalities , could rather be traced to a higher dose of steroids . Moreover , the triple drug therapy was more efficacious than any double drug regimen in the prevention of chronic histological changes in renal allografts .
85964
Intervention_Pharmacological
immunosuppressive regimens
85965
Intervention_Pharmacological
different immunosuppressive regimens
85966
Intervention_Pharmacological
cyclosporine
85967
Intervention_Pharmacological
azathioprine
85968
Intervention_Pharmacological
methylprednisolone
85969
Intervention_Pharmacological
Aza plus CsA
85970
Intervention_Pharmacological
Aza plus MP
85971
Intervention_Pharmacological
CsA plus MP
85972
Intervention_Pharmacological
Aza plus CsA
85973
Intervention_Pharmacological
Aza plus MP
85974
Intervention_Pharmacological
CsA plus MP
85975
Intervention_Pharmacological
Aza plus MP
85976
Intervention_Pharmacological
steroids
85977
Intervention_Pharmacological
Aza plus MP
85978
Intervention_Pharmacological
triple therapy
85979
Intervention_Pharmacological
cyclosporine-related
85980
Intervention_Pharmacological
steroids
85981
Intervention_Pharmacological
triple drug therapy
85982
Outcome_Adverse-effects
Long-term consequences
85983
Outcome_Adverse-effects
long-term effects
85984
Outcome_Mortality
graft survival rates
85985
Outcome_Mental
chronic rejections
85986
Outcome_Other
graft function
85987
Outcome_Physical
posttransplantation diabetes mellitus
85988
Outcome_Physical
abnormal glucose tolerance test
85989
Outcome_Physical
cholesterol level
85990
Outcome_Physical
lipid abnormalities
85991
Outcome_Physical
disturbances in glucose metabolism
85992
Outcome_Other
histological changes
85993
Outcome_Mental
CsA-specific changes
85994
Outcome_Physical
isometric vacuolation in tubuli
85995
Outcome_Other
Histological alterations characteristic of chronic rejection
85996
Outcome_Other
" chronic allograft damage index . " Chronic allograft damage index
85997
Outcome_Mental
histopathological change
85998
Outcome_Adverse-effects
cyclosporine-related side-effects
85999
Outcome_Adverse-effects
posttransplant diabetes mellitus
86000
Outcome_Adverse-effects
some lipid abnormalities
86001
Outcome_Physical
chronic histological changes in renal allografts
86002
Participant_Condition
renal allografts
86003
Participant_Sample-size
128
86004
Participant_Condition
first cadaveric renal allograft
86005
Participant_Sample-size
98
86006
Participant_Condition
did not have type I or II diabetes