OPDC's professionals are responsible for the clinical development of several compounds. OPDC is engaged in clinical testing of compounds intended for the treatment of polycystic kidney disease.

Polycystic Kidney Disease is the most common genetic, life threatening disease affecting more than 600,000 Americans and an estimated 12.5 million people worldwide - regardless of sex, age, race or ethnic origin. In fact, PKD affects more people than cystic fibrosis, muscular dystrophy, hemophilia, Down syndrome and sickle cell anemia — combined.

Polycystic means multiple cysts. In effect, PKD denotes multiple cysts on each kidney. These cysts grow and multiply over time, also causing the mass of the kidney to increase. Ultimately, the diseased kidney shuts down causing end-stage renal disease for which dialysis and transplantation are the only forms of treatment.

A cyst in the kidney begins as an outpouching of the nephron, similar to a blister. Cysts can occur anywhere on the length of the nephron. Although polycystic means many cysts, not every nephron forms cysts. The fluid inside the cysts often reflects the area in the nephron from which the cyst arose.

Approximately 70 percent of cysts detach from the nephron when they are still very small, about 2 mm (1/8 inch) in diameter. Over time the cysts enlarge and can become filled with clear fluid or fluid that contains blood or white blood cells.

Cysts can form in other organs as well as the kidney; the most common other site is the liver. Current research suggests that liver cysts are associated with the bile ducts or tubules of the liver rather than liver cells themselves. It appears that rather than take the place of functioning liver cells, cysts merely push the liver cells aside. This is why liver cysts don't cause liver failure even though the liver can become quite enlarged due to cysts.

Research has shown that there are at least three components to cyst formation:

1. Cell proliferation: The cells of a cyst wall reproduce themselves more than do normal kidney cells. This makes the cysts grow in size.

2. Cellular secretion: Secretion is a way of making fluid. To form a cyst the cells themselves must produce fluid. If there were no fluid produced to fill the cyst, there would merely be a ball of cells.

3. Abnormal basement membrane: The basement membrane is a very thin layer of tissue the cyst cells sit on. In ADPKD this layer is thicker than usual and is made up incorrectly.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common, affecting 1-in-400 to 1-in-500 adults. Autosomal Recessive Polycystic Kidney Disease (ARPKD) is far less common, affecting 1-in-10,000 at a far younger age, including newborns, infants and children.

Autosomal recessive Polycystic Kidney Disease (ARPKD), sometimes called "infantile PKD," is a genetic disease that is inherited in a random fashion that is beyond a parent's control. In recessive disorders such as ARPKD, the baby must inherit a copy of the disease gene from each parent in order to be affected. ARPKD affects one in 10,000 to one in 40,000 babies, and often causes significant mortality in the first month of life.

If the infant survives the newborn period, the chances of survival are good. For the child who survives the first year of life, the probability of not reaching end-stage renal failure is 67 percent at 15 years of age. Of those who survive the newborn period, approximately one-third will need dialysis or transplantation by 10 years of age.

Symptoms

Early in the disease there generally are no symptoms at all. In fact, many people are never diagnosed with ADPKD because they have so few or no symptoms. Often the first sign of ADPKD is high blood pressure, blood in the urine or a feeling of heaviness/pain in the back, sides or abdomen. Sometimes the first sign is urinary tract infection and/or kidney stones.

High blood pressure, or hypertension, affects about 60 percent to 70 percent of people with ADPKD. High blood pressure begins early in the course of ADPKD. In ADPKD it seems that the most likely reason for high blood pressure is the constricting of blood vessels. In ADPKD, cysts can press on blood vessels in the kidney, resulting in decreased blood flow to some parts of the kidney. Sensors in the nephron react as though the blood pressure in the kidney was low; renin is then secreted, which in turn generates angiotensin, constricting the blood vessels, and causing high blood pressure. If not treated, hypertension damages the kidneys, enlarges the heart and can cause strokes.

Chronic pain is one of the most common problems for people with ADPKD. The pain is usually in the back or the side and occasionally in the stomach. The pain can be intermittent and mild requiring only occasional mild pain medicine such as acetaminophen. In a small number of people, the pain can be constant and quite severe.

Close to 50 percent of those with ADPKD have had or will have blood in their urine at some time. This is called hematuria. The urine may look pink, red or brown. Passing small amounts of red blood cells in the urine that can only be seen under a microscope may also occur. This is called microscopic hematuria. Blood in the urine can last for a day or less or the bleeding may go on for days. Strict bed rest, increased fluid intake, and acetaminophen (if there is pain) are usually the treatments if the bleeding is prolonged.

Urinary tract infection, commonly called UTI, is an infection caused by bacteria that have reached the bladder, kidneys or the cysts themselves. The infection usually starts in the bladder and can progress up the ureters into the kidneys. Although both men and women have UTIs, they are far more common in women. UTIs are quite common in the general population, but they appear to be more frequent in those with ADPKD. The most common symptom of UTI is pain or burning with urination and/or an urgent need to urinate even though there is only a small amount of urine. When the infection is in the kidney or in a cyst, there may be a sudden onset of fever, chills and back or flank pain.

Kidney stones occur in about 20 percent to 30 percent of people with ADPKD compared to 8 percent to 10 percent in the general population. One reason kidney stones are more common may be due to cysts blocking the tubules, preventing normal drainage. When the urine stays in one area longer than it should, crystals can form and cause kidney stones. Another reason that stones may form in some people with ADPKD is that there is a decrease in urine citrate. Urine citrate is a substance that prevents formation of kidney stones. The symptoms of kidney stones are severe pain in the back, side or into the groin. Often there will be blood in the urine when passing a kidney stone.

Although everyone with the ADPKD gene develops kidney cysts, not everyone progresses to kidney failure, and if they do it's rarely before the age of 40.

Source: PKD Foundation www.pkdcure.org

To learn more about clinical trials being conducted by Otsuka, please visit the U.S. National Institute of Health clinical trials registry website, www.clinicaltrials.gov.