Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of morbidity and is 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 uniquivocal 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 to intervene upon. TKV ultimately may be used as a surrogate marker of disease progression in clinical trials. The goals of CRISPIN extend the observations of CRISPI/II. 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 to improve genotype/phenotype and biomarker studies.
Aim 5. Determine whether intensive dietary counseling and intervention in a small group of CRISP participants is successful in modifying the relatively fixed pattern of sodium intake observed in CRISPI and reducing the rate of growth of the polycystic kidneys.

Public Health Relevance

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 efficiency of therapy/drug development and result in increased life expectancy and improved quality of life in patients with ADPKD.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK056956-14
Application #
8704919
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Flessner, Michael Francis
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Chapman, Arlene B (2014) The importance of quantifying genetic heterogeneity in ADPKD. Kidney Int 85:236-7
Bae, Kyongtae T; Sun, Hongliang; Lee, June Goo et al. (2014) Novel methodology to evaluate renal cysts in polycystic kidney disease. Am J Nephrol 39:210-7
Bae, Kyungsoo; Park, Bumwoo; Sun, Hongliang et al. (2013) Segmentation of individual renal cysts from MR images in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 8:1089-97
Boertien, Wendy E; Meijer, Esther; Li, Jie et al. (2013) Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort. Am J Kidney Dis 61:420-9
Kistler, Andreas D; Serra, Andreas L; Siwy, Justyna et al. (2013) Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study. PLoS One 8:e53016
Bae, Kyongtae T; Tao, Cheng; Wang, Jinhong et al. (2013) Novel approach to estimate kidney and cyst volumes using mid-slice magnetic resonance images in polycystic kidney disease. Am J Nephrol 38:333-41
Chapman, Arlene B; Bost, James E; Torres, Vicente E et al. (2012) Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 7:479-86
Chapman, Arlene B (2012) The fetal environment: a critical phase that determines future renal outcomes in autosomal dominant polycystic kidney disease. Kidney Int 81:814-5
Torres, Vicente E; Grantham, Jared J; Chapman, Arlene B et al. (2011) Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6:640-7
Chapman, Arlene B; Wei, Wenjing (2011) Imaging approaches to patients with polycystic kidney disease. Semin Nephrol 31:237-44

Showing the most recent 10 out of 23 publications