About Inherited Kidney Disease due to Mutations in Renin

mucin1_kd

Mucin-1 Kidney Disease

Also sometimes known as:

Medullary Cystic Kidney Disease Type 1

What are the signs of this disease?

There are several common features of this disease: 

  1. Anemia beginning in childhood that improves when children enter adolescence.
  2. Mildly low blood pressure
  3. Mild elevations in potassium
  4. Gout occurring at a young age in some individuals
  5. An increased risk of developing acute kidney failure in childhood.
  6. Slowly progressive chronic kidney disease leading to the need for dialysis or kidney transplant between 40 and 70 years.   
  7. Family history

(1) Patients are often identified in childhood with anemia (low hemoglobin level).  The cause of the anemia often cannot be identified, except for the fact that serum erythropoietin levels are low. 

(2)  Patients may have a mildly low blood pressure. 

(3)  Patients may have an elevated serum potassium level and are sometimes prescribed a low potassium diet.  

(4) Affected inidviduals or some member of their family often develop gout.  Gout is a type of arthritis (joint inflammation) caused by high blood uric acid levels.  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. 

(5) Patients sometimes develop acute kidney failure in childhood.  This may occur after a viral illness (such as the flu or a bad case of diarrhea) or after a lot of physical activity (like running a race in hot weather).  Patients receive supportive treatment for this and kidney function recovers. 

(6)  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 40 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.  A blood creatinine level above 1 mg/dl (or international units: 88 mmol/L) means that the  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.  Urine testing in affected individuals shows little protein and blood in the urine. This is often confusing to the patient’s doctor because blood and protein in the urine are found in most kidney diseases. 

(7)  Inherited kidney disease due to mutations in renin is an inherited disorder.  If a person has the disease, his 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:

The patient is a young woman in overall good health.  When her hemoglobin was tested as an infant, it was found to be low.  A complete workup – including a bone marrow biopsy – did not reveal a cause.  The patient was started on erythropoietin shots and the anemia improved.  At 6 years of age she had the flu.  She became dehydrated and was found to be in kidney failure.  She was admitted to the hospital and her kidney function recovered. However, a year later, lab testing revealed that her creatinine level was a little bit high.  Further testing showed she had a relatively low blood pressure, and her serum potassium was mildly elevated at 5.5 (normal < 5).  She then developed gout at age 15.  The patient’s doctor was uncertain what caused the elevation in serum creatinine, as the urine showed no blood or protein, and the kidney ultrasound was normal.  The patient’s mother had received a kidney transplant at age 40, and the patient’s grandfather had required dialysis at 60 years of age.  There were several cousins, aunts, and uncles who also had an elevated serum creatinine.  A kidney biopsy was performed that showed “interstitial scarring” – scarring in the middle of the kidney.  None of the kidney doctors could give a name to the cause of the kidney disease.

What causes inherited kidney disease due to mutations in renin?

Renin is a hormone in the body that helps to regulate blood hemoglobin levels, blood pressure, blood potassium levels, and blood flow to the kidney.  In this condition, one of the genes making renin is abnormal, while the other is normal.  Affected individuals make less than a normal amount of renin, resulting in mildly low blood pressure, low hemoglobin (anemia), mildly elevated potassium and elevated uric acid levels.  An abnormal form of renin is also made.  This abnormal form deposits within tubular cells of the kidney, leading to slowly progressive kidney disease.  

Everyone has two genes that each make a renin molecule.  One gene is inherited from the father, and one is inherited by the mother.  It only takes one abnormal gene (either from the father or mother) to inherit this condition.

What about research?

The cause of this condition was identified by Drs. Martina Zivna and Stanislav Kmoch at the First Faculty of Medicine of the Charles University, in Prague, the Czech Republic.  Dr. Bleyer at Wake Forest identified families with the disorder and havebeen working with Dr. Kmoch’s team to study this condition.

How can I find out if I have the disease?

Please 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 ableyer@wakehealth.edu  .

What can I do if I find out I have the disease?

It is important to see a kidney doctor if you have this condition.  A high sodium diet – or a medicine called fludrocortisone – can help to treat the low blood pressure and the high potassium levels in this disorder.  Allopurinol or febuxostat are medicines that can be given to prevent gout.  Erythropoietin can be given to treat the anemia, though some individuals do not require this medicine.

Our goal at Wake Forest School of Medicine is to increase understanding about inherited kidney disease due to renin mutations.  We are studying the effect of a high sodium diet and fludrocortisone on the progression of this disease.  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.  This condition is very rare, and we are trying to work with more families with this condition.

Research Update:

We are trying to study the effect of a high sodium diet and fludrocortisone on this condition.  If you think or know you have inherited kidney disease due to a renin mutation, please contact us at ableyer@wakehealth.edu 

If you have any questions concerning this condition, please contact us at (336)-716-4513.

 

Last Updated: 08-25-2016
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