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Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function
1Department of Nephrology, Hospital Prínceps de Espanya, Ciutat Sanitària i Universitària de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain.
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.
Insights
Mycophenolate mofetil (MMF) allows a reduction in cyclosporine (CsA) dosage, improving kidney function and lowering TGF-beta1 levels in renal transplant recipients. This approach effectively manages hypertension without increasing rejection risk.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation Medicine
Background:
- Cyclosporine (CsA) nephrotoxicity presents as functional impairment and chronic renal damage.
- Overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine, is linked to CsA-associated renal fibrosis.
- Mycophenolate mofetil (MMF) offers a potential strategy to reduce CsA dosage without compromising graft survival.
Purpose of the Study:
- To evaluate the impact of MMF combined with CsA dose reduction on renal function and TGF-beta1 levels.
- To assess the safety and efficacy of this immunosuppressive regimen in long-term renal allograft recipients with suspected CsA nephrotoxicity.
Main Methods:
- 16 renal allograft recipients with suspected CsA nephrotoxicity were enrolled.
- MMF (2 g/day) was introduced, and CsA dose was adjusted to achieve target whole-blood levels (40-60 ng/ml) within one month.
- Renal function, CsA levels, and plasma TGF-beta1 were monitored before and 6 months after MMF initiation.
Main Results:
- MMF facilitated a significant reduction in mean CsA dose and blood levels.
- Associated improvements included decreased serum creatinine, increased glomerular filtration rate, and enhanced renal plasma flow.
- Plasma TGF-beta1 levels decreased significantly, correlating with reduced CsA levels. No rejection episodes occurred, and blood pressure improved.
Conclusions:
- MMF enables CsA dose reduction, leading to improved renal function and reduced TGF-beta1 production in renal transplant patients.
- This therapeutic strategy also aids in better hypertension control.
- The combination therapy demonstrated short-term efficacy without an increased risk of acute rejection.