Successful therapy with tacrolimus and mycophenolate mofetil in Chinese renal allograft recipients with C4d–positive chronic rejection

Ji Shuâ€“Ming; Chen Jinâ€“Song; Wen Jiâ€“Qiu; Cheng Dongâ€“Rui

Volume : VI, Issue : IV, April - 2016

Successful therapy with tacrolimus and mycophenolate mofetil in Chinese renal allograft recipients with C4d–positive chronic rejection

Ji Shu Ming , Chen Jin Song, Wen Ji Qiu , Cheng Dong Rui

Abstract :

Objective To investigate the efåcacy of combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) rescue therapy for C4d–positive chronic rejection of renal transplants. Methods Thirty six of these patients were prospectively enrolled in the present analysis. Male 15, female 21, mean age 34.6±12.9 years. Criteria for inclusion were C4dpositive chronic rejection. Basal immunosuppression was changed in 36 recipients, including conversion from cyclosporine A to TAC (at initial dose of 0.15mg /Kg per day, and the dose was subsequently adjusted to maintain FK506 whole blood through levels between 5–10μg/L. Results After 3–year of follow–up, protienuria after FK506 conversion had reduced from (3.7±1.2) g/24hr. to (0.9±0.4 g/24hr), P <0.001. Serum creatinine(SCr) levels after TAC conversion had reduced from (3.1 ±1.2)mg/dl to (1.8 ±0.6) mg/dl, P <0.001. Among the thirty–six patients with improvement in the rate of decline of renal function, twenty–three patients(63.9%) had their regression lines become positive and eight patients(22.2%) had their regression lines become less negative. Five patients(13.8%) had increased rate of decline in renal function with their regression lines becoming more negative. By 3–year follow–up, pathological changes had been signiåcantly improved in accordance with the 97‘ Banff classiåcation: renal tubular atrophy (52.8% vs 44,4%), interstitial åosis (50.0% vs 30.6%) and arterial hyaline degeneration (52.8% vs 25.0%). Transplant renal pathological suggests chronic damage index (CADI) are: 8.3 ± 2.6 and 3.0 ± 0.7. Repeated renal biopsy revealed that 22 cases (61.1%) became C4d negative in renal tissue and no case become positive, and 14 case (38.9%) showed steady C4d positive accompany with hepatitis C (renal graft biopsy showed memanous nephropathy) after the switch TAC. Classiåcation according to the Banff 07 criteria: 22 cases of C4d0,5 cases of C4d1, the 5 cases of C4d2, 4 cases of C4d3. During the follow–up of 3 years, C4d turn negative 22 cases (61.1%), and weakened C4d 5 cases (13.9%), C4d for 4 cases (11.1%) were positive. After the treatment with TAC, with the disappearance of C4d deposition in allograft, HLA–II class antibody levels decreased from 57 ±9% (35–87.5%) to 6.1 ± 1.2% (3.9–7.3%). No deaths and no new acute rejection during the 3–year follow–up. 2 cases concurrent with BK virus nephropathy, the other 3 cases of initial SCr > 4.0 mg/dl, eventually leading to renal allograft loss return dialysis. Graft survival rate was signiåcantly increased in TAC treatment (93.5%) follow–up 3–year. Conclusion The optimal treatment for alloantibody mediated C4d–positive chronic rejection remains undeåned. Our åndings suggest that combining TAC–MMF treatment represents a powerful immunosuppressive regimen that limits both T–cell and B–cell responses. In such a combination protocol, not only effective control of antidonor antibody production but also improvement of long–term graft survival may be achieved.