Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease.
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 % 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% in MMF-treated Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42% and 43%, 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 % in vehicle-treated Cy/+ rats, 45.2% in MMF-treated Cy/+ rats (P<0.05), 32.9% and 37.7% 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.


CONCLUSIONS
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.
Division of Nephrology, Nephrology Institute of PLA, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Tong
T
Zhang
Li
L
Wang
Xishan
X
Xiong
Zhiguo
Z
Mao
Liming
L
Wang
Changlin
C
Mei
D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage*; D013997:Time Factors
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus