The following articles on Autosomal Dominant Polycystic Kidney Disease (ADPKD) have recently been published in medical journals.  These articles were written by investigators from the PKD Research Group and are based on the research studies being conducted at the University of Colorado Health Sciences Center. 

Recurrence of Intracranial Aneurysms in Autosomal-Dominant Polycystic Kidney Disease
Kidney International 2003; 63:1824-1830
Belz MM, Fick-Brosnahan GM, Hughes RL, Rubinstein D, Chapman AB, Johnson AM, McFann KK, Kaehny WD, Gabow PA.

We examined twenty people with ADPKD who had previously been diagnosed with an intracranial aneurysm to see whether they had developed any new aneurysms or if an existing aneurysm had increased in size. Four of eleven subjects (36%) who had a previous ruptured aneurysm had a new aneurysm on re-study, and one of nine subjects (11%) with a previous aneurysm diagnosed through screening had a new aneurysm on re-study. Two of the subjects with new aneurysms also had an increase in size of a previously diagnosed aneurysm. Previous studies at the University of Colorado have shown that intracranial aneurysms occur in about 5% of people with ADPKD, and the incidence is higher in people with a family history of ruptured intracranial aneurysm.
 

Epidemiological Study of Kidney Survival in Autosomal Dominant Polycystic Kidney Disease
Kidney International 2003; 63:678-85
Schrier RW, McFann KK, Johnson AM.

This study demonstrated that both men and women with PKD examined at the University of Colorado between 1992-2001 were able to live longer without needing dialysis or a kidney transplant than patients examined between 1985-1992. The improvement in the later group is attributed to better blood pressure control and more frequent use of angiotensin-converting enzyme inhibitors (a type of blood pressure medication). Additionally, blood pressure and renal volume growth were highly predictive of end-stage renal disease (needing dialysis or a transplant). Male patients with blood pressures greater than 120/80 mm Hg were 6.1 times more likely to enter end-stage renal disease than male patients with blood pressures lower than 120/80 mm Hg. Likewise, female patients with blood pressures greater than 120/80 mm Hg were 2.3 times more likely to enter end-stage renal disease than female patients with blood pressures lower than 120/80 mm Hg.

Cardiac and Renal Effects of Standard Versus Rigorous Blood Pressure Control in Autosomal Dominant Polycystic Kidney Disease: Results of a Seven-Year Prospective Randomized Study
Journal of the American Society of Nephrology 2002; 13:1733-9
Schrier RW, McFann KK, Johnson AM, Chapman AB, Edelstein CL, Fick-Brosnahan GM, Ecder T.

High blood pressure can sometimes result in an enlargement of the left side of the heart. People with this enlargement of the heart are more likely to have cardiac problems such as heart attacks and heart failure. This 7-year study demonstrated that rigorous blood pressure control (less than 120/80 mm Hg) was more effective in reversing this type of heart enlargement than standard blood pressure control (135-140/85-90 mm Hg) in people with PKD, high blood pressure, and heart enlargement. We also found a greater reduction in heart size with a type of blood pressure medication called an angiotensin-converting-enzyme inhibitor (ACE inhibitor) than with another type of blood pressure medication, a calcium channel blocker. This study provides critical information for doctors caring for PKD patients with high blood pressure since cardiac complications are the leading cause of death for these patients. We did not see a difference in kidney function between those treated with rigorous compared with standard blood pressure control. A larger study may be able to determine if rigorous blood pressure control has any beneficial effect on kidney function.


Relationship Between Renal Volume Growth and Renal Function in Autosomal Dominant Polycystic Kidney Disease: A Longitudinal Study
American Journal of Kidney Diseases 2002; 39:1127-34
Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW.

This study suggests that people with PKD whose kidneys are enlarging at a fast rate will have poor kidney function before those whose kidneys are not enlarging so fast. This is important for future research studies in PKD, because we would like to try new treatments to slow kidney growth in people who still have good kidney function.

Caspases, Bcl-2 Proteins and Apoptosis in Autosomal Dominant Polycystic Kidney Disease
Kidney International 2002; 61:1220-30
Ecder T, Melnikov VY, Stanley M, Korular D, Lucia MS, Schrier RW, Edelstein CL.

This research demonstrated that there is a greater percentage of programmed cell death (called apoptosis) in the kidneys of rats with PKD than in the kidneys of rats without PKD. The study also demonstrated that the mechanisms that control apoptosis are significantly different in PKD rats than in normal rats. Understanding the process that controls programmed cell death in PKD may lead to new treatments for PKD in humans.

Progression of Autosomal Dominant Polycystic Kidney Disease in Children
Kidney International 2001; 59:1654-62
Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA.

We measured the kidneys of 182 children under the age of 18 with PKD to determine how fast the kidneys enlarge in children with PKD. We found that boys and girls had similar kidney sizes, so the larger kidneys seen in grown men as compared with grown women must occur after childhood. Children with high blood pressure had larger kidneys than children with normal blood pressure. Almost all the children we studied had normal kidney function.

Familial Clustering of Ruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease
American Journal of Kidney Diseases 2001; 38:770-6
Belz MM, Hughes RL, Kaehny WD, Johnson AM, Fick-Brosnahan GM, Earnest MP, Gabow PA.

Ruptured intracranial aneurysms (bursting blood vessels in the brain caused by weak spots in the wall of the blood vessel) are very traumatic events, causing death or significant brain damage in many sufferers. About 5 to 10% of people with PKD have an intracranial aneurysm that may burst, compared with about 1% of people without PKD. We had noted a few families where more than one person with PKD in the family had suffered a ruptured intracranial aneurysm, and we wondered if it was due to chance, or if some families were more likely to have ruptured intracranial aneurysms than others. Our analysis showed that it was not due to chance, and thus if you have PKD and one of your family members experienced a ruptured intracranial aneurysm, you should have an imaging study of your head (usually magnetic resonance angiography) to determine if you have an intracranial aneurysm.

Hypertension in Autosomal Dominant Polycystic Kidney Disease: Early Occurrence and Unique Aspects
Journal of the American Society of Nephrology 2001; 12:194-200
Ecder T, Schrier RW.

High blood pressure occurs in approximately 60% of people with PKD before kidney function becomes impaired. High blood pressure is related to faster progression to kidney failure and heart disease. Heart problems are common in people with PKD. Many people with PKD die from heart problems such as heart attacks. But, high blood pressure can be treated. Early treatment of high blood pressure is very important to increase the life span of those with PKD and to decrease the risk of heart problems.

Diuretics Versus Angiotensin-Converting-Enzyme-Inhibitors in Autosomal Dominant Polycystic Kidney Disease
American Journal of Nephrology 2001; 21:98-103
Ecder T, Edelstein CL, Fick-Brosnahan GM, Johnson AM, Chapman AB, Gabow PA, Schrier RW.

Two types of blood pressure medicines, diuretics and angiotensin-converting-enzyme inhibitors (ACE inhibitors), are often used to control high blood pressure. In this study, we compared the research records of a small number of people with PKD who had taken one or the other of these drugs (but not both) over several years. Although both types of drugs reduced blood pressure, we found that kidney function declined more in people taking diuretics than in people taking ACE inhibitors. This suggests that blood pressure control with an ACE inhibitor may be better than with a diuretic for people with PKD, but this study needs to be confirmed by a larger study.

Von Hippel-Lindau Disease Masquerading as Autosomal Dominant Polycystic Kidney Disease.
American Journal of Kidney Diseases 2001; 37:852-8
Chatha RK, Johnson AM, Rothberg PG, Townsend RR,Neumann HPH, Gabow PA.

Many people with PKD have no family history of PKD. In some cases the parents are not available to be tested for PKD, and in some cases the parents do not have cysts (or have very few cysts), meaning the person with PKD has a new mutation. One woman in our study with no family history of PKD but many cysts was thought to have PKD. This is the most common diagnosis in people with many cysts, even without a family history, because PKD is the most common cystic kidney disease, and we know that new mutations often occur in PKD. It was later determined that this woman did not have ADPKD, but had another disease called von Hippel-Lindau disease. We tried to determine if there were any clues we missed that could have pointed to the correct diagnosis. The woman had several cysts in her pancreas, which are uncommon in PKD but frequent in von Hippel-Lindau disease. Therefore, we recommend that doctors should screen for manifestations of von Hippel-Lindau disease in people with renal cysts and pancreatic cysts but no family history of PKD.

Effect of Antihypertensive Therapy on Renal Function and Urinary Albumin Excretion in Hypertensive Patients With Autosomal Dominant Polycystic Kidney Disease
American Journal of Kidney Diseases 2000; 35:427-32
Ecder ST, Edelstein CL, Chapman AB, Johnson AM, Tison L, Gill E, Brosnahan GM, Schrier RW.

In this study we compared the effects of two medications for high blood pressure on both kidney function and urinary protein excretion in PKD patients with high blood pressure but good renal function. The two drugs compared were amlodipine (a calcium channel blocker) and enalapril (an angiotensin-converting enzyme inhibitor). We found that blood pressure control of less than 140/90 mm Hg with either medication was associated with a smaller loss in kidney function than shown in previous studies with PKD patients. Patients on enalapril had lower urinary albumin excretion levels than patients on amlodipine. Early treatment of high blood pressure may slow the progression of renal disease in patients with PKD.
 

Revised: 06/09/03.