Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.
BACKGROUND
Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection.


METHODS
We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-beta1, production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-beta1 levels were evaluated before and 6 months thereafter.


RESULTS
MMF allowed a decrease in both the mean dose of CsA (3.8+/-1.35 vs. 2.2+/-0.73 mg/kg/day; P<0.01) and CsA levels (148+/-36 vs. 53+/-19 ng/ml; P<0.001). The reduction of CsA was associated with a decrement of serum creatinine levels (210+/-46 vs. 172+/-41 micromol/L; P<0.001) and an increase in both the glomerular filtration rate (32.9+/-12 vs. 39.1+/-14 ml/min/1.73 m2; P<0.02) and renal plasma flow (195+/-79 to 218.6+/-74.02 ml/min/1.73 m2; P<0.02). There was a reduction in plasma TGF-beta1 levels (4.6+/-4.2 vs. 2.0+/-1.4 ng/ml; P=0.003) and CsA levels correlated with TGF-beta1 (r=0.536, P=0.002). No rejection episodes occurred, and an improvement in both systolic (149+/-13 vs. 137+/-12 mmHg; P<0.01) and diastolic blood pressure (89+/-14 vs. 83+/-10 mmHg; P<0.04) were observed.


CONCLUSIONS
These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.
Hueso
M
M
Department of Nephrology, Hospital Prínceps de Espanya, Ciutat Sanitària i Universitària de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain.
Bover
J
J
Serón
D
D
Gil-Vernet
S
S
Sabaté
I
I
Fulladosa
X
X
Ramos
R
R
Coll
O
O
Alsina
J
J
Grinyó
J M
JM
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D009173:Mycophenolic Acid