Uromodulin Kidney Disease (UKD) is also known as:

  • Medullary Cystic Kidney Disease Type 2
  • Familial Juvenile Hyperuricemic Nephropathy
  • Familial Gouty Nephropathy
  • Glomerulocystic Kidney Disease
  • Familial Gout-Kidney Disease
  • UMAK

UKD is considered a rare disease. There are about 400 families worldwide that have been identified with this disease. 

In UKD, patients slowly lose kidney function over time. The kidneys are bean-shaped organs, about the size of a fist.  They are located in the back next to the spinal column. Healthy kidneys filter and clean about 200 quarts (liters) of blood every day, removing excess water, minerals, and wastes. The kidneys also produce hormones that make red blood cells and control blood pressure.  They make active Vitamin D, which the body uses to keep your bones strong.

Kidney failure is usually determined by a blood test, called the blood creatinine level. Creatinine is a waste product that your muscles produce as they work. Healthy kidneys will filter creatinine into the urine, while damaged ones will not.  Because damaged kidneys cannot filter creatinine well, it stays in the bloodstream and the blood creatinine level rises.

Blood creatinine is part of a group of tests that may be done as part of a routine physical or before surgery. UKD may be first identified when an elevated creatinine is found on a routine blood test.
In UKD, blood creatinine levels rise slowly over years as the kidneys become more damaged. Once the levels rise to a certain level, usually above about 6 mg/dL (milligrams per deciliter) or about 530 mmol/L (millimoles per liter), the patient must begin dialysis or have a kidney transplant.

In UKD, the kidney also has difficulty removing uric acid. This results in a buildup of uric acid in the bloodstream and high blood uric acid levels. These high uric acid levels can cause gout.

How Will Uromodulin Kidney Disease (UKD) Make Me Feel?

Many people do not even know they have a kidney disease until their blood creatinine levels rise very high and they lose a lot of kidney function.  They usually do not develop any symptoms until the disease is very advanced.  They then become more tired than usual and just start to not feel so good.  Their appetite may worsen.  When kidney disease gets worse, patients like to keep the room warmer than usual.  They often develop anemia.

In UKD, gout can develop after age 15 in SOME individuals.  Gout can be treated with medications such as allopurinol or febuxostat.  If patients take one of these medicines daily, they will never have gout again after about six months.  If patients do not take one of these medicines, they can develop worsening gout over the course of their levels.  

Causes of Uromodulin Kidney Disease (UKD)

There 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.

Symptoms of Uromodulin Kidney Disease (UKD)

There are three common features of this disease:

  • 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.

  • 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.
  • 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.

What can I do for my health if I have UKD?

Currently there is no known treatment for UKD, and the only cure is a kidney transplant. However, there is still a lot that you can do to stay healthy if you have UKD:

  • Do not go on a low-sodium (salt diet), as this can make gout work or increase the blood uric acid.  
  • If you have gout, consider taking febuxostat or allopurinol. Discuss this with your doctor.  These agents will prevent gout.
  • Do not smoke.  Smoking makes every type of kidney disease get worse more quickly.  It also causes hardening of the arteries and lung disease.  The combination of kidney disease and smoking is not good.  Thus, it is important to stop smoking if you do smoke.  Children of affected MKD patients should be encouraged to never start smoking.
  • Check blood pressure regularly.  As kidney disease worsens, blood pressure can increase.  This rise in blood pressure can lead to a higher risk of heart disease, strokes and heart attacks.  If your blood pressure is high, you should get it treated.  You should work with your doctor to keep it under good control.
  • Stay in shape and keep weight under control.  Being very overweight can makmore difficult to do the surgery for a kidney transplant.  You should watch your weight closely.6.  
  • See a kidney doctor to help manage gout and complications of kidney disease.
  • If you have poor kidney function, work on getting a kidney transplant before you have the need for dialysis.

Typical Patient Case 

The 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 disease.

Investigation 

This 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.

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.

What Can I Do If I Have Uromodulin Kidney Disease (UKD)?

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.

Our goal at CepEsperu School Baptist 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.