Statin Therapy in Patients with Early-Stage ADPKD
Abstract
This proposal will investigate a new potential treatment to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Our study will specifically address the Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Area of Polycystic Kidney Disease (PKD). The program has identified the development of improved treatment strategies for PKD as a gap and priority research area; our proposed clinical study will investigate the use of statin drugs to slow the progression of ADPKD. If successful, this will offer an improved treatment strategy in a disease for which current treatment options are extremely limited. ADPKD is a severe genetic disorder that afflicts between 1/400 to 1/1000 individuals. Based on a current estimate of 2.2 million active and reserve military personnel, this translates into 5,000 military personnel who may have ADPKD even without inclusion of their family members. There is no treatment or cure for PKD. ADPKD costs the military and other federal health programs, such as the Veterans Health Administration (VHA), more than $2 billion annually for dialysis, transplantation, and related therapies. ADPKD is characterized by progressive enlargement of the kidney, caused by growth of fluid-filled cysts that originate from the part of a nephron that leads away from the glomerulus, leading to crowding of normal kidney tissue and eventually kidney failure. To date within the U.S., there are no clinically approved treatments to slow progression of kidney disease progression in ADPKD. In 50% of patients, loss of kidney function requiring dialysis or transplantation occurs by age 60. Therefore, testing valid treatment interventions to reduce both hospitalization and deaths related to kidney disease progression in ADPKD is of high priority. The proposed research will determine the effectiveness of statin therapy (i.e., a type of cholesterol lowering drug) for slowing kidney growth and improving kidney function in adult patients with ADPKD. The study also will provide insight into how statin therapy improves kidney health by determining the physiological mechanisms (biological reasons) involved. If the outcome of this proposal is successful, it will provide clinicians an important, inexpensive, and safe new treatment to slow kidney disease progression, thus preserving kidney function. In addition, understanding how statin therapy provides this protective effect will allow the scientific community to better understand ADPKD as a disease state. The tasks for this project include performing a randomized controlled study, a rigorous scientific clinical study, to examine using statin therapy in ADPKD patients. We will include 150 adults with ADPKD but who are not yet in kidney failure. These patients will be randomly assigned to receive a statin (Pravastain 40 mg daily by mouth) or a placebo (?sugar pill?), which looks identical to the statin, for 2 years. Research participants will be given appointments to undergo a magnetic resonance imaging (MRI) and a Glofil-125 (Iothalamate I-125 injection), which will provide precise information on the size of the kidney, blood flow through the kidney, and kidney function. We will measure and compare kidney size and function between the two groups after 2 years of treatment. The data will be analyzed to determine if the use of the statin had a more significant effect on kidney growth and kidney function than the placebo pill. During the course of the study, investigators will collect blood and urine samples from participants in both groups, which will allow them to examine if the statin, when compared to placebo, had an effect on inflammation, cell proliferation, and other important signs of ADPKD. We are testing the effects of statin therapy because an earlier study showed that these drugs are effective in children with ADPKD, but they have not yet been studied in adults with ADPKD. We expect that adults with ADPKD who are treated wi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710382
Entities
People
- Michel Chonchol
Organizations
- United States Army
- University of Colorado Denver