Table 1.

mTOR inhibition in animal models of PKD

Drug dose	Model	Duration of treatment	Outcome	Blood levels (ng/mL)	Side effects	Ref
Sirolimus 0.2 mg/kg/d IP	Male Han:SPRD	Age 4–8 wk	Decreased kidney enlargement and cyst volume. Improved kidney function.	Not reported	Reduced body weight by 22%	[25]
Sirolimus 2 mg/kg/d orally	Male Han:SPRD	3 mo	Decreased kidney enlargement and cyst volume. Improved kidney function.	0.5–1.9	No change in body weight	[26]
Everolimus 3 mg/kg/d orally	Male Han:SPRD	5 wk	Decreased kidney enlargement and cyst volume. Improved kidney function.	5–7	Impaired weight gain	[27]
Sirolimus 5 mg/kg/d IP	orpk rescue mouse	Age 150–178 d	Decrease in cyst volume.	Not reported		[28]
Sirolimus 5 or 1.67 mg/kg/d IP	bpk mouse	Age 7–21 d	Decrease in cyst volume. Normalization of kidney function.	Not reported		[28]
Sirolimus 0.2 mg/kg/d IP	Male Han:SPRD	Age 1–12 mo	Normalized kidney volume, renal function, blood pressure and heart weight.	6.6–6.9.	Reduced body weight by 11%	[29]
Sirolimus 0.2 mg/kg/d IP	Female Han:SPRD rat	Age 4–12 wk	No effect on kidney and cyst volume.	5.9	Reduced body weight by 15%	[30]
Sirolimus 5 mg/kg/d IP.	Pkd1 knockout	Age 28–49 d	Reduced cyst growth. Preserved renal function.	Not reported		[31]
Sirolimus 0.5 mg/kg/d IP	Pkd2 knockout	Age 4–16 wk	Reduced kidney size and cyst volume. No effect on kidney function.	22	No change in body weight	[32]
Everolimus 3 mg/kg orally	Male Han:SPRD	4–9 wk treatment (pulse). 4–16 wk treatment (continuous).	Both regimens reduced cyst volume and improved kidney function.	4.7–6.2	Impaired weight gain	[33]
Sirolimus 2 mg/kg orally	pck rat	4, 8, or 12 wk	No effect on liver and kidney cysts	0.6	Reduced weight gain	[34]
Low dose (10 mg/kg) vs. High dose (100 mg/kg) orally	Pkd1 knockout mice	Early vs. late treatment	Low dose did not affect renal cysts. Early treatment was better than late treatment.	3 vs. 30–60	Not reported	[35]