Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease

ABSTRACT

Objective: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss of renal function and cyst progression compared to rapamycin in Han SPRD rats. We also sought to assess whether the effect of combination therapy of MMF plus rapamycin was better than that of monotherapy. Methods: Sixty heterozygous (Cy/+) and littermate control (+/+) male Han SPRD rats were weaned at 4 weeks of age, then divided into four groups randomly to receive different treatments by intragastric administration for 2 months vehicle-treated group as control, MMF-treated group (20mg/kg/day), rapamycin-treated group (2mg/kg/day), and MMF+Rapa- treated group (MMF 20mg/kg/day plus Rapamycin 2mg/kg/day). Resulls After 2 months of treatment, rapamycin caused a 22 percent decrease in body weight in comparison to the control group, whereas MMF had no significant effect on weight gain. The steady increase of BUN in Cy/+ rats was reduced by 15 percent in MMF-treated Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42 percent and 43 percent, respectively. CCr was 0.93±0.11ml/min in vehicle-treated Cy/+ rats, 1.67±0.23 ml/min in MMF-treated Cy/+ rats (P<0.05), 1.72±0.44 ml/min and 1.83±0.21 ml/min in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (.P<0.01). Cyst volume density was 57.1 percent in vehicle-treated Cy/+ rats, 45.2 percent in MMF-treated Cy/+ rats (P<0.05), 32.9 percent and 37.7 percent in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (P<0.01). MMF markedly ameliorated interstitial inflammation and fibrosis. Rapamycin showed a similar effect on interstitial inflammation and fibrosis, but to a lesser degree. Conclusion: MMF is more tolerable than rapamycin and can retard deterioration of renal function in Han SPRD rats, though its effect is weaker than that of rapamycin. Combination therapy does not exert more favorable effect than monotherapy.