This newsletter is a work in progress. It will be completed and mailed once we have a start date for the HALT PKD Study. Please register to be on our Mailing List for the latest information regarding PKD or PKD Research studies at the University of Colorado Health Sciences Center.

In July 2002 we began the 18th year of PKD Research at the University of Colorado Health Sciences Center. Currently, we are conducting four major studies supported by the National Institutes of Health: Project 1 is a randomized trial of anti-hypertensive therapy in children, adolescents and young adults with PKD. Project 2 is focused on the identification of modifying genes in PKD. The premise is that identifying genes that promote disease severity will help us to understand the mechanisms of ADPKD and will also allow selection of high-risk patients for treatment trials. Projects 3 and 4 complement the two clinical investigations by performing basic science studies which have clinical implications for patients with ADPKD. Project 3 investigates the role of caspase inhibitors in apoptosis (programmed cell death) in rodent models of ADPKD, and Project 4 examines liver cystic disease. With early diagnosis and interventions, ADPKD patients are expected to live longer, a setting whereby the problems relating to massive liver cysts will increase. Very little is known about liver cysts and thus focused interventions are not possible. A fifth study is in the planning stages: The HALT PKD Study which will be conducted here and at 3 other centers around the country. The administration and data management section supports all of these studies. These studies are described in more detail below.

We are conducting this study of children to determine if treatment with a particular type of blood pressure medication currently on the market, an angiotensin converting enzyme inhibitor (ACEI), will slow renal cyst growth in the children and young adults with PKD. Eighty-nine children and young adults, age 4 to 21 years, have enrolled in this study. Enrollment is now complete.

One third of the children in the study had high blood pressure at the start of the study (above the 95^th percentile for their age and height). These children are all treated with anti-hypertensive medications. The goal for half of the children is to lower their blood pressure to below the 50^th percentile, and the goal for the other half of the children is to lower their blood pressure to below the 90^th percentile (the usual goal for children with high blood pressure). Another third of the children in the study had borderline high blood pressure at the start of the study (above the 75^th percentile for their age and height, but below the 95^th percentile). Half of these children are treated with anti-hypertensive medications to lower their blood pressure to below the 50^th percentile, and the other half of the children do not receive medication unless their blood pressure goes above the 95^th percentile. The final third of the children in the study had normal blood pressure at the start of the study (below the 75^th percentile for their age and height). Half of these children are treated with anti-hypertensive medications and the other half of the children do not receive medication unless their blood pressure goes above the 95^th percentile.

The goal of this study is to see if the children receiving treatment (or more intensive treatment) will have less kidney growth than the children not receiving treatment (or less intensive treatment. We suspect that it may be necessary to start treatment early in people with PKD, because often the kidneys grow very large before the person has symptoms like pain or problems with their kidney function. If we can slow down the kidney growth it may prevent these problems later on.

We are currently conducting a study of modifier genes (or non-PKD genes) that may affect the course of PKD. These are genes such as those involved in high blood pressure or cell growth.

In the past we have studied many families with PKD. One of the most important things we have learned is that there is a large amount of variability both between and within families in the way PKD is expressed.

We have used this knowledge to come up with some ideas about the possible reasons for this variability. We are now looking into these possible reasons for variability in hopes of learning more about the way the severity of PKD varies from person to person, and how genetic and environmental factors may affect this.

Apoptosis is the programmed death of cells within the body. A group of proteins called caspases is involved in the process of apoptosis.

In people with PKD, apoptosis is thought to play a role in the loss of normal cells in the kidney and it is this loss of normal cells which causes the kidney itself to become damaged and ultimately non-functional.

In this study, we plan to examine the kidneys of rats and mice with different types of PKD to try to find how apoptosis takes place in the kidneys and how it can be stopped.

The long-term goal of this study is to learn how apoptosis and caspases play a role in the course of human PKD and hopefully to change the course of the disease through the new knowledge obtained.

J. Gregory Fitz; R. Brian Doctor, PhD; Kimberly Leslie, MD

The presence of cysts in the liver is one of the most common ways PKD manifests in the body outside of the kidneys.

The long-term goal of this study is to learn the reason for the development of liver cysts in people with PKD and with that knowledge move toward learning what the medical community can do to diminish or prevent liver cyst growth.

We are examining the livers of rats and mice with PKD, but we are also examining tissue from human livers and fluid from human liver cysts. If you or a family member with PKD are having surgery to remove all or part of a cystic liver, please give us call if you’d like to donate tissue and/or fluid. Please call us ahead of time so we can work out the details with your doctor.

Linda Perkins (administrator) and Ann Johnson (statistician and data manager) are likely the voices you hear on the phone when you call the PKD office. Linda and Ann have both been with the PKD study for a number of years and in that time they have seen a number of changes in the treatment and lives of PKD patients. They hope to see more positive strides as the PKD study continues into another year.

Linda continues to be responsible for making the office run as smoothly as possible. Recently Diana George has assisted in scheduling patient travel and in-patient studies for the Children’s High Blood Pressure Study.

The families with ADPKD who have been studied for more than 30 years at the University of Colorado continue to be a unique resource for the study of human ADPKD. All of the data collected from each study, questionnaire, etc. are entered into a database for analysis.

Craig Edelstein is currently is his junior year of college where he is studying information systems. Although Craig is staying very busy with school he continues to assist in the office during his breaks from school.

We are excited to welcome Dr. Melissa Cadnapaphornchai as Co-Investigator of the Children’s High Blood Pressure Study. Dr. Cadnapaphornchai, Assistant professor of Pediatrics and Medicine earned her medical degree at the University of Michigan Medical School in 1993. She completed her residency here at the University of Colorado Health Sciences Center. She is Board-Certified in Medicine.

The High Blood Pressure Study attempted to answer these two questions:

1. Which level of blood pressure control is best for people with PKD and high blood pressure? The two levels of control are either "standard" (130/85-140/90) or "strict" (120/80 or lower).

2. Is an angiotensin converting enzyme inhibitor such as Enalapril or a calcium channel blocker such as Amlodipine more effective in controlling high blood pressure in people with PKD?

If you, your family or employer wish to make donations to further PKD research,

please consider the group here:

PKD Research

University of Colorado Health Science Center

4200 East Ninth Avenue #C283

Denver, CO 80262

(303) 315-7821

or the national foundation:

Polycystic Kidney Research Foundation (PKRF)

4901 Main St., Suite 320

Kansas City, MO 64112-2674

1-800-PKD-CURE

Our newest project is the design and distribution of a questionnaire regarding the time of onset of the first symptoms of ADPKD, family clustering of symptoms and severity of ADPKD, and trends in diagnosis. This questionnaire was sent to over 1500 ADPKD patients in order to gain new understanding of the variation in time of onset of ADPKD, early manifestations of the disease, and the progress in early diagnosis of the disease. We have received more than 600 completed questionnaires.

We would like to thank every-one who has kept us informed about their new address when they have moved. Only by studying the same people at different times can we see how PKD affects people over time. It would also be helpful if you would send us your new phone number when you move. Some people whom we've studied in the past and we would like to study again have moved and left no forwarding address. We will be contacting relatives of these people to see if they can help us get in touch with them.