The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) formed the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) in March 1999 via a cooperative agreement mechanism. The five-year prospective cohort study will determine whether changes in anatomic characteristics of the kidneys of patients with PKD as measured by radiologic imaging techniques will be useful in providing surrogate measures for disease progression.
Comprising four participating clinical centers and a data-coordinating and imaging-analysis center, the consortium has developed and is implementing studies nationwide to test whether imaging techniques can provide accurate and reproducible markers of progression of renal disease in patients with polycystic kidney disease (PKD). Participating clinical centers are Emory University, the Mayo Clinic, University of Kansas, and the University of Alabama at Birmingham. The data coordinating and imaging analysis center is at Washington University. The primary objectives of this investigation are as follows:
- Develop and test the accuracy and reproducibility of imaging techniques to monitor changes in renal cyst size and parenchymal involvement in well-characterized cohorts of patients with PKD to assess their utility as surrogate markers of disease progression
- Establish and maintain a database of uniformly and accurately collected information including renal functional parameters and other selected markers of disease progression identified by both the data-coordinating and imaging-analysis center and the participating clinical centers
- Correlate parenchymal involvement with renal functional changes in PKD patients with various rates of progression
- Maintain and make available such data to facilitate the planning and implementation of clinically appropriate interventions in the near future
Polycystic Kidney Disease Research
Polycystic kidney disease is a serious and costly disease. About 500,000 people in the United States have PKD, and it is the fourth leading cause of end-stage renal failure in the nation. The important advances in understanding the molecular basis of adult dominant PKD (ADPKD1 and ADPKD2) have generated intense interest and have provided investigators with important research opportunities. Although certain topics are already receiving careful study, timely opportunities to discover more about the natural history of PKD and appropriate clinical interventions to ameliorate its course need to be addressed. Such investigations are likely to generate, in the foreseeable future, a variety of possible strategies for clinical intervention.
Several previous studies have established typical rates of decline of glomerular filtration rate (GFR) in PKD patients. Patients with PKD genotypes vary in their rate of progressive loss of renal function. Nevertheless, through much of the course of PKD, GFR is maintained, and detectable decreases in GFR occur relatively late in the natural history of the disorder. Therefore, a clinical investigation to attempt to alter the decline of GFR can only be undertaken late in the disease. Furthermore, although functionally a critical parameter, GFR is cumbersome to assess. Therapeutic interventions are likely to be targeted to patients at highest risk for the development of progressive deterioration of renal function. Methods to identify such patients and monitor markers of progressive disease are critical to the development of early, effective interventions.
The focus of CRISP is investment in the groundwork that will facilitate the development and eventual testing of clinically practical intervention strategies. For example, current state-of-the-art methods using magnetic resonance imaging (MRI) techniques with rapid image acquisition rates make possible high resolution three dimensional images of the kidneys. Semi-automated image analysis algorithms also exist to determine renal size and the portion of the kidney occupied by cystic structures.
Some experience has been gained in establishing that repeat imaging of the same PKD patient, using these techniques, yields reproducible estimates of kidney size and the proportion of renal parenchyma occupied by cysts. MRI may also have the advantage of permitting simultaneous estimation of GFR. Ultrasound has the advantage of being more cost-effective and perhaps more acceptable to patients for repetitive studies, but the measurements may be less accurate and reproducible. Nonetheless, there is very limited experience in applying these techniques to follow progression of the renal disease. Development of improved, reproducible imaging methods that assess cyst growth and provide markers of disease progression could markedly improve the feasibility of clinical trials.
CRISP's overall goal is to develop methods that would facilitate shortening the observation period necessary to determine efficacy of treatment interventions in PKD patients. Specific goals of this study are as follows:
- Quantify cyst growth and ascertain severity of renal parenchymal involvement by sequential measurement of total kidney volume and the ratio of intact parenchyma to renal parenchyma occupied by cysts over time
- Establish useful clinical correlations of imaging data with other markers of disease progression
- Identify and test other potential markers or indices of disease progression, e.g., assessment of loss of heterozygosity of renal cells shed in the urine, or other markers, in cohorts of patients with PKD
- Gain information about the cost-effectiveness, patient acceptability, and advantages and disadvantages of different imaging techniques used serially in patients with PKD.
Over the five-year period of CRISP, several cohorts of patients, at different stages of disease, and with varying rates of disease progression, will be studied in interrelated investigations.
Program Officer: John Kusek, Ph.D., 301-594-7717.