Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

This study is a prospective, randomized, open-label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD). Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit. General Procedures: In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.