Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in individuals with autosomal dominating polycystic kidney disease (ADPKD). progression in ADPKD. Method/design This single center randomised controlled open BMS-777607 label trial assesses the restorative effect security and tolerability of the mTOR inhibitor sirolimus (Rapamune?) in individuals with autosomal dominating polycystic kidney disease and maintained renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary end result guidelines will become preservation of renal function security and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time display whether treatment with sirolimus efficiently retards cyst growth in individuals with ADPKD. Trial sign up “type”:”clinical-trial” attrs :”text”:”NCT00346918″ term_id :”NCT00346918″NCT00346918 Background Autosomal dominating polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage renal disease (ESRD) influencing all ethnic organizations worldwide with an incidence of 1 1 in 500 to 1 1 in 1000 [1]. ADPKD is definitely characterized by the progressive development of countless cysts in both kidneys which distort the normal kidney architecture and prospects to a loss of renal function. The development of renal failure is definitely highly variable but typically individuals develop ESRD by the age of 40 to 50 years necessitating renal alternative therapy (RRT) and/or kidney transplantation [2]. Apart from blood pressure control and symptomatic treatment of cyst bleedings and infections Rabbit polyclonal to IQGAP3. there is no curative therapy for this disease [3]. PKD1 and PKD2 encode the proteins polycystin-1 and polycystin-2 which are indicated in the kidney and function collectively to regulate growth and morphologic construction of renal epithelial cells [4]. Mutation in PKD1 prospects BMS-777607 to a more severe phenotype of ADPKD than mutations in PKD2 with ESRD happening on average 20 years earlier (53.4 versus 72.7 years) [5]. In ADPKD progressive cyst growth generally precedes the development of renal insufficiency. Compensatory mechanisms (hyperfiltration) preserve renal function virtually normal for decades despite continuous cyst growth. By the time renal function starts to BMS-777607 decrease the kidneys are usually grossly enlarged with little normal renal parenchyma recognisable on imaging studies. Data from your consortium for radiologic imaging studies of polycystic kidney disease (CRISP) while others have shown the rate of kidney volume growth is definitely a predictor of renal practical decline and therefore kidney volume is used as surrogate marker of disease progression especially in medical intervention tests for ADPKD [6 7 Non-invasive radiologic methods are available to monitor the growth rate of kidney volume. Renal ultrasound measurements are operator-dependent and not exactly reproducible. Unenhanced and contrast enhanced Computer tomography (CT) scanning is reported to be an accurate method to determine kidney volume but it entails ionizing radiation and potentially nephrotoxic contrast medium and is consequently not an ideal method in individuals with reduced kidney function needing repeated measurements [8 9 Due to its high smooth tissue contrast and the lack of ionizing irradiation Magnetic resonance imaging (MRI) is also considered useful to monitor kidney volume changes in ADPKD. The analysis of sequential MRI scans was shown to be accurate to monitor rates of kidney volume enlargement in ADPKD [7]. Sirolimus is an immunosuppressant that binds to FK Binding Protein-12 (FKBP-12) and inhibits the activation of the mTOR a key regulatory kinase of growth and proliferation. Sirolimus is definitely approved BMS-777607 for the prevention of graft rejection following renal transplantation. Due to its antiproliferative properties it is also used in coated stents to prevent coronary artery restenosis after angioplasty [10]. Furthermore it has shown clinical performance in kidney transplant recipients with Kaposi’s sarcoma [11]. We have shown previously the mTOR inhibitors rapamycin and everolimus efficiently reduce cyst growth and loss of renal function in an experimental animal model for PKD [12 13 Additional studies have shown that rapamycin is also effective.