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.
Zhang
Tong
T
Division of Nephrology, Nephrology Institute of PLA, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Wang
Li
L
Xiong
Xishan
X
Mao
Zhiguo
Z
Wang
Liming
L
Mei
Changlin
C
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