Uromodulin Kidney Disease
Uromodulin Kidney Disease
goal at Wake Forest School of Medicine is to help one patient, one family at at
time. We are trying to increase
understanding about UMAK. We are committed to finding a cure for this
condition. Finding a treatment will require studying the urine and DNA of
as many affected individuals as possible. If you or someone you know has
this condition, we hope that you will consider getting in touch with us to be
part of our study. Working together, we believe that we will be able to
find an effective treatment.”-- Anthony J. Bleyer, MD, Professor, Section of
Nephrology, Department of Internal Medicine
Also sometimes known as:
Medullary Cystic Kidney Disease Type 2
Familial Juvenile Hyperuricemic Nephropathy
Familial Gouty Nephropathy
Glomerulocystic Kidney Disease
Familial Gout-Kidney Disease
What are the signs of this disease?
There are three common features of this disease:
(1) Patients develop chronic kidney failure with loss of kidney function beginning in the teenage years and progressing to the need for dialysis or kidney transplantation at an age between 30 and 70 years. Patients have few or no symptoms of kidney disease when they are diagnosed.
Usually, affected individuals are found to have some loss of kidney function when they undergo blood testing by their doctor as part of a general health screening. A blood test called the serum creatinine level is performed. If the blood creatinine level is above 1, this is usually abnormal and means the kidney is not removing the creatinine from the blood well enough. In patients with this condition, the serum creatinine is measured by their doctor and is elevated. Frequently the doctor does not know why the serum creatinine level is high. Even if a kidney biopsy (the removal of a small piece of kidney tissue) is performed, a correct diagnosis is frequently not made.
(2) The patient has gout or some member of the family has a history of gout. Gout is a type of arthritis (joint inflammation) caused by high blood uric acid levels. Affected individuals have high blood uric acid levels, and this leads to gout. Every affected individual in the family may not have gout, but there are usually at least one or two people in the family who have gout. Gout frequently involves the big toe, the foot, or the knee. The big toe will become extremely tender, and even placing a sheet on the toe will cause pain. In this condition, gout occurs in the late teenage years in both men and women. (In contrast, gout developing in the normal adult population tends to occur in overweight men in their 30’s to 50’s.) Family members may develop bumps on their joints called tophi that are deposits of uric acid.
(3) The disease is likely to be inherited. If a person has the disease, their children have a 1 out of 2 (50%) chance of having the disease. The disease does not skip a generation, though a parent may be less severely affected than their child, and may not have gout or other signs of kidney disease for some time. Therefore, there is usually a strong family history of the condition.
The following is an example of a typical patient case:
patient is a healthy woman in overall good health. At the age of
seventeen, she developed a bout of severe pain in her right big toe. This
pain lasted for a week. The patient knew this was gout because her
father, two uncles, and her grandmother had gout. Her grandmother died of
kidney failure many years ago, and her father had a kidney transplant and was
doing well. She went to see her doctor who told her that she had
gout. He was confused as to why she had gout—she was young and was a
woman. He also did not know why so many family members had kidney
disease. He ordered a blood uric acid level and a blood creatinine
level. The blood uric acid level came back high, and the blood creatinine
level was 1.8 (greater than 1 which is abnormal). He did a kidney biopsy
which showed “interstitial nephritis (inflammation of the inside of the
kidney)”. Later, another doctor suggested that she have a blood test to
see if she had the gene for a disease called uromodulin associated kidney
disease. She had the test done and found that she suffered from the
What causes Uromodulin Kidney Disease (UKD)?
is a protein that is normally made by kidney cells called uromodulin (also
known as Tamm Horsfall Protein). This is the most common protein found in
the urine of healthy people. It was discovered by Drs. Tamm and Horsfall
about fifty years ago, and has been studied for many years, but no one knows
what it does. The protein is normally made by kidney cells and then
enters the urine.
In UKD, there is a small change in the gene that makes the protein. This
change in the gene causes a change in the amino acids that make up the
protein. This results in the protein not being built normally. When
the protein cannot be built normally, it precipitates abnormally in the cell
and forms deposits. It is thought that these deposits slowly result in
kidney cell death. Eventually, these changes lead to kidney failure.
Everyone has two genes that each make a uromodulin molecule. One gene is
inherited from the father, and one is inherited by the mother. It only
takes one abnormal gene to get the disease. This is because the abnormal
protein that is made interferes with the machinery that the cell uses to make
the uromodulin protein.
What about research?
section describes the research that has occurred in this disease over
time. The first paper ever written on this was by Duncan and Dixon who
described a family with gout and kidney failure. Drs. Simmons and Cameron
described a number of families suffering from this condition, and showed that a
high blood uric acid level and low urine uric acid were the first signs of the
disease and occurred in early childhood. Thereafter, several groups were
able to link the disease to a certain area of the chromosome. Drs. Dahan
and Hildebrandt then postulated that, based on genetic analysis, medullary
cystic kidney disease type 2 and familial juvenile hyperuricemia were two
different names given to the same disease. In 2003, Drs. Hart and Bleyer
identified a mutation in the gene encoding uromodulin as the cause of these
diseases. In 2004, a test became available by Athena Diagnostics so that
individuals could be tested for the disease.
How can I find out if I have the disease?
contact us if you think you may have this condition, and we can help you find a
diagnosis. We would also be most interested to hear from you or your doctor if you think
that you have the disease to help you find out more about your condition.
Please email us at firstname.lastname@example.org.
What can I do if I find out I have the disease?
It is important to see
your family doctor or a kidney doctor to help follow your
kidney function. Taking a medicine called allopurinol may slow the
progression of kidney failure and will prevent gout from becoming severe.
goal at Wake Forest School of Medicine is to increase understanding about UKD.
We are committed to finding a cure for this condition. Finding a
treatment will require studying the urine of as many affected individuals as
possible. If you or someone you know has this condition, we hope that you
will consider getting in touch with us. Working together, we believe that
we will be able to find an effective treatment.
Is there a booklet I can read about
We have a
booklet available which can be downloaded here: UKD Booklet for Patients
What is the latest news?
We are currently still examining urine samples to determine the concentration of the uromodulin protein in the urine. Learning about this protein in the urine will help us to better understand the disease.
We have currently identified the condition in eight families in the United States.
We are trying to obtain as many measurements of blood uric acid and serum creatinine as possible from patients who have had the disease for a long time. This will help us to determine how fast the disease progresses.
If you have any questions concerning this condition, please contact us at (336)-716-4513.