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 Imaging Studies of Polycystic Kidney Disease (CRISP I);in 2006, the University of Pittsburgh replaced Washington University for CRISP II. The primary objectives of CRISP I 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 follow up in 200 CRISP l/ll participants, we now can: 1) establish an uniquivocal relationship between TKV and qualitative (patient reported outcomes) and quantitative (renal insufficiency) end-ppints;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 CRISP III extend the observations of CRISP l/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 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 CRISP I and reducing the rate of growth of the polycystic kidneys.
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.
|Heyer, Christina M; Sundsbak, Jamie L; Abebe, Kaleab Z et al. (2016) Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 27:2872-84|
|Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie et al. (2016) Mutations in GANAB, Encoding the Glucosidase IIÎ± Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease. Am J Hum Genet 98:1193-207|
|Kim, Youngwoo; Ge, Yinghui; Tao, Cheng et al. (2016) Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol 11:576-84|
|Irazabal, MarÃa V; Rangel, Laureano J; Bergstralh, Eric J et al. (2015) Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol 26:160-72|
|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|
|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|
|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|
|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|
|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|
|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|
Showing the most recent 10 out of 19 publications