Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Currently there is no treatment for ADPKD other than supportive care and blood pressure control. Usually dialytic treatment or renal transplantation becomes necessary when the disease has progressed to end-stage renal failure.We and others could demonstrate that rapamycin, a classical mTOR inhibitor, retards cyst growth and preserves renal function in a rodent model of ADPKD. The aim of our study is to investigate whether Rapamune (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. We anticipate that we can slow disease progression and delay the need for chronic renal replacement therapy by the inhibition of mTOR with Rapamune. This is a 24-month prospective, controlled, open label study with 2 parallel groups in patients with ADPKD. Patients will be randomized at a 1:1 ratio to one of the 2 treatment arms. Primary endpoint is percentage change of renal volume measured by high resolution magnetic resolution imaging.

Inclusion criteria

• Male or female ADPKD patient between 18 and 40 years of age
• measured GFR higher than 70 ml/min 1.73m2
• documented kidney volume progression
• informed consent

Exclusion criteria

• Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
• increased liver enzymes (2-fold above normal values)
• hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
• granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3),
• infection with hepatitis B or C, HIV
• any past or present malignancy
• mental illness that interfere with the patient ability to comply with the protocol
• drug or alcohol abuse within one year of baseline
• co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
• co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
• known hypersensitivity to macrolides or Rapamune