The majority of patients with autosomal dominant polycystic kidney disease (ADPKD types 1 and 2) and autosomal recessive polycystic kidney disease (ARPKD) develop end-stage renal failure. Preliminary studies indicate an inverse correlation between the volume of cystic kidneys and their function reflected in the GFR. However, there is presently no way to determine early in the course if an individual with PKD is destined to experience renal failure in a normal life expectancy. To meet the objectives of the RFA we will develop a PCC to evaluate the following specific aims:
Aim 1. Assemble a cohort of individuals with well-characterized PKD (ADPKD) who are at relatively high risk to experience progression to end-stage-renal disease (ESRD). ADPKD subjects will be selected from the region who have one or more risk factors for progression, including: family history of ESRD, male gender, multiple pregnancies, hypertension, proteinuria and hematuria. ARPKD subjects will be selected primarily from those who have survived without dialysis beyond the first year of life.
Aim 2. Compare and evaluate the accuracy and reproducibility of renal images obtained by rapid acquisition MR, ultrasound and CT in representative examples of PKD. These studies will be done in phantom models of cystic kidney in order to determine optimum precision and accuracy of each method in comparison to the other, and in selected patients with renal cystic changes ranging from mild to severe. PKD subjects will then be studied serially as outlined in the next aim.
Aim 3. Evaluate sequential changes in renal morphometrics in subjects with PKD in relation to other surrogate markers for progressive disease. Subjects will be imaged at predefined intervals in order to determine: a) The rate of change in total kidney volume, total cyst volume and total parenchymal volume; b) The rate of change of """"""""functional"""""""" parenchymal volume; c) The rate of change of individual cyst volume; d) The intra- renal distribution of cysts in relation to progression factors; e) Changes in the expression of surrogate markers of disease progression in relation to renal enlargement and parenchyma volume, and ; f) the relation of cyst growth to hypotheses of intra-cyst fluid accumulation. Successful completion of these studies will identify clinically reliable methods for determining the rate of progression of PKD before there are measurable changes in GFR and irreversible changes in renal ultra- structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK056943-05S1
Application #
6950565
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Flessner, Michael Francis
Project Start
2000-02-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2005-11-30
Support Year
5
Fiscal Year
2004
Total Cost
$100,000
Indirect Cost
Name
University of Kansas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
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Kim, Youngwoo; Bae, Sonu K; Cheng, Tianming et al. (2016) Automated segmentation of liver and liver cysts from bounded abdominal MR images in patients with autosomal dominant polycystic kidney disease. Phys Med Biol 61:7864-7880
Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie et al. (2016) Mutations in GANAB, Encoding the Glucosidase II? Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease. Am J Hum Genet 98:1193-1207
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