Autosomal dominant tubulointerstitial kidney disease

Other Names: ADTKD; Autosomal dominant medullary cystic kidney disease; MCKD; Autosomal dominant medullary cystic kidney disease (former)

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of genetic kidney diseases that cause progressive loss of kidney function.

Cause

ADTKD is caused by mutations in certain genes. These gene problems are passed down through families (inherited) in an autosomal dominant pattern. This means the abnormal gene is needed from only one parent in order to inherit the disease. Often, many family members have the disease. With all forms of ADTKD, as the disease progresses, the kidney tubules are damaged. These are the structures in the kidneys that allow most water in the blood to be filtered and returned to the blood.

Their abnormal genes that cause the different forms of ADTKD are:

• UMOD gene -- causes ADTKD-UMOD, or uromodulin kidney disease
• MUC1 gene -- causes ADTKD-MUC1, or mucin-1 kidney disease
• REN gene -- causes ADTKD-REN, or familial juvenile hyperuricemic nephropathy type 2 (FJHN2)
• HNF1B gene -- causes ADTKD-HNF1B, or maturity-onset diabetes mellitus of the young type 5 (MODY5)

When the cause of ADTKD is not known or a genetic test has not been done, it is called ADTKD-NOS.

Types

There are 3 known subtypes of ADTKD, which are classified based on their genetic causes and presence of additional features:

UMOD-related autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) or uromodulin kidney disease (formerly known as UMOD-associated kidney disease, familial juvenile hyperuricemic nephropathy type 1, medullary cystic kidney disease type 2 (MCKD2), and uromodulin storage disease)- caused by a mutation in the UMOD gene. This is the most common subtype. The age of onset varies but kidney problems are usually noted in adolescence,and may progress to end-stage renal disease (ESRD) between the fourth and seventh decades of life. High levels of uric acid in the blood (hyperuricemia) and gout (a form of arthritis), sometimes occur as early as the teenage years.

REN-related autosomal dominant tubulointerstitial kidney disease (ADTKD-REN) (previously known as "familial juvenile hyperuricemic nephropathy type 2") - caused by a mutation in the REN gene. Kidney disease is usually present in childhood. Many people with this subtype also have anemia in childhood (even before kidney disease begins), low or low-normal blood pressure, mildly high levels of potassium in the blood (hyperkalemia), hyperuricemia and gout.

MUC1-related autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1) or Mucin-1 kidney disease or MKD (formerly known as medullary cystic kidney disease type 1) - caused by a mutation in the MUC1 gene. It is characterized by slowly progressive disease that leads to end-stage renal disease (ESRD) occurring at any age between 20 and 70 years. There are no other systemic features in addition to chronic kidney disease, although some develop gout in adulthood.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Inheritance of ADTKD is autosomal dominant, as the name implies. Most people with ADTKD have a family history of "kidney disease" (if not a family history of ADTKD specifically) or some of the other symptoms.

Signs and symptoms

Early in the disease, depending on the form of ADTKD, symptoms may include:

• Excessive urination (polyuria)
• Gout
• Salt cravings
• Urination at night (nocturia)
• Weakness

As the disease worsens, symptoms of kidney failure may develop, which include:

• Easy bruising or bleeding
• Fatigue, weakness
• Frequent hiccups
• Headache
• Increased skin color (skin may appear yellow or brown)
• Itching
• Malaise (general ill feeling)
• Muscle twitching or cramps
• Nausea
• Pale skin
• Reduced sensation in the hands, feet, or other areas
• Vomiting blood or blood in the stool
• Weight loss
• Seizures
• Confusion, decreased alertness, coma

Diagnosis

The health care provider will examine you and ask about your symptoms. You'll likely be asked if other family members have ADTKD or kidney disease.

Tests that may be done include:

• 24-hour urine volume and electrolytes
• Blood urea nitrogen (BUN)
• Complete blood count (CBC)
• Creatinine blood test
• Creatinine clearance -- blood and urine
• Uric acid blood test
• Urine specific gravity (will be low)

The following tests can help diagnose this condition:

• Abdominal CT scan
• Abdominal ultrasound
• Kidney biopsy
• Kidney ultrasound

Treatment

There is no cure for ADTKD. At first, treatment focuses on controlling symptoms, reducing complications, and slowing the progression of the disease. Because so much water and salt are lost, you will need to follow instructions on drinking plenty of fluids and taking salt supplements to avoid dehydration. As the disease progresses, kidney failure develops. Treatment may involve taking medicines and diet changes, limiting foods containing phosphorus and potassium. You may need dialysis and a kidney transplant.

Prognosis

The age at which people with ADTKD reach end-stage kidney disease varies, depending on the form of the disease. It can be as young as in the teens or in older adulthood. Lifelong treatment may control the symptoms of chronic kidney disease.

NIH genetic and rare disease info

• NIH info on Autosomal dominant tubulointerstitial kidney disease

Autosomal dominant tubulointerstitial kidney disease is a rare disease.

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