Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of morbidity and the fourth leading cause of ESRD in the world, affecting more than 500,000 U.S. citizens. Researchers at the University of Alabama, Emory University, University of Kansas, Mayo Clinic and Washington University joined together in 2000 to create the Consortium for Radiologic Studies of Polycystic Kidney Disease (CRISPI) and in 2006 included the University of Pittsburgh in place of Washington University for CRISP II. The primary objectives of CRISPI and II were to: establish accurate, reliable and reproducible magnetic resonance based measurements of total kidney volume (TKV), liver cyst volume (LCV), renal blood flow (RBF), and patterns of cyst growth and expansion. Based on 7.3 years of longitudinal followup in 200 CRISP l/ll participants, we can now: 1) establish an unequivocal relationship between TKV and qualitative (patient reported outcomes) and quantitative (renal insufficiency) end-points;as well as 2) identify potential modifiable risk factors associating with TKV and LCV for intervention studies. TKV ultimately may be used as a surrogate marker of disease progression in clinical trials. The goals of CRISPIN extend the observations of CRlSPI/ll. The overarching Aim for CRISP III is to develop and enhance prediction models that best predict renal insufficiency in ADPKD. Specifically, Aim 1: Extend the serial quantification of TKV and LCV to develop and test new models for predicting the risk of developing renal insufficiency.
Aim 2 : Determine the extent to which age and sex-adjusted measurements of RBF predict the rate of change in TKV and determine if RBF and TKV independently predict the risk of developing renal insufficiency.
Aim 3 : Develop methods to quantify the influence of renal cyst number, volume, and topography at baseline on the subsequent course of TKV and GFR and the risk of developing renal insufficiency.
Aim 4 : Expand and analyze CRISP biological samples collected in NIDDK repositories to improve genotype/phenotype and biomarker studies, and facilitate ancillary studies.
Aim 5 : Test the feasibility and efficacy of intensive dietary counseling in modifying the fixed pattern of sodium intake observed in CRISP and determine if this change alters the rate of TKV change.
The results of these studies will impact the lives of patients with ADPKD. Developing predictive markers of disease severity early, prior to loss of renal insufficiency will result in increased life expectancy and improved quality of life in patients with ADPKD.
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