Kidney research UK

ADTKD-UMOD BASICS

Dr Holly Mabillard began by clarifying that the name for the condition was only agreed a few years ago. It was previously known as

• Medullary cystic kidney disease type 2
• Familial juvenile hyperuricaemia nephropathy type 1
• Uromodulin-associated kidney disease

AD – Autosomal Dominant – describes how the condition is inherited

T – Tubulointerstitial – refers to the part of the kidney it effects, the area where salt and water are exchanged

There are seven categories of ADTKD. They are categorised according to the mutation they cause. In this condition the gene is called UMOD.

What does the UMOD gene do?

It makes a protein called uromodulin in the kidneys. Uromodulin is secreted into the kidney where it forms a gel like structure. This gel protects the kidney from bacteria in the urinary tract, prevents the formation of kidney stones and stops salt from leaking into the kidney.

When there is a mutation in the UMOD gene, the DNA code makes faulty uromodulin. As the protein can’t move into the urine, it builds up in the kidney and forms a scarring called ‘fibrosis’.

ADTKD is classed as a rare disease. It effects 9/million people but is thought to be underdiagnosed. It accounts for 2% of people with CKD and 1% of people with CKD stages 3-5. It is the third most common inherited kidney disease.

Signs and Symptoms?

Most people will have a normal kidney size and no blood or protein in their urine.

Gout

50% of women with the gene and 70% of men will have gout. This can occur at a young age and due to a build up of uric acid in joints.

Cysts & Salt Wasting

Small kidney cysts may be present but are asymptomatic. This is usually something mild such as an irregular kidney outline or a slight dilation of the cavity in the inner kidney through which urine passes. There is often evidence of salt wasting or loss early in the condition. Symptoms of this may include low blood pressure and feeling light-headed.

Children may have a history of bed-wetting.

Kidney Failure

The median (average) age of kidney failure is 47 years but this ranges from 18-88 years. Some with the mutation may never develop kidney failure. This is assessed by measuring creatinine in the blood and using this to measure the ‘eGFR’ which predicts the percentage of kidney function remaining. Dialysis is usually necessary when this reaches around 6%. Symptoms will include

• Shortness of breath
• Tiredness
• Loss of appetite
• Swelling in the feet and ankles
• Nausea and vomiting
• Weight loss
• Headache
• Itch
• Bad breath

ADTKD can affect both men and women. It does not skip a generation, but family members can present with different symptoms. It is diagnosed using a genetic test which is usually taken from a blood sample but can be a cheek swab.

Diagnosis

This is performed by taking a family history. Other tests may include a urinalysis and an ultrasound scan and blood will be taken for genetic testing. A biopsy is not necessary for diagnosis if the genetic test is positive. Having a genetic result is also important for future trials into the condition.

Treatment

Losartan is the medication most recommended for lowering BP and reducing the amount of protein in the urine although others from the same class of drug may be prescribed.

Slow sodium may be prescribed to help symptoms of salt wasting.

Medications such as allopurinol or febuxostat can be prescribed to treat symptoms of gout.

ADTKD does not recur after kidney transplant as the new kidney will make its own unaffected uromodulin.

Resources

• RaDaR Registry | The UK Kidney Association RaDaR is a registry of all patients in the UK with a rare kidney disease. You may have been recruited to it by your local kidney team. It is overseen by the UK Kidney Association. As well as providing data on how people with rare kidney conditions present and what happens to them, it also allows researchers to contact you with any research opportunities that may be relevant to you.
• Home | Kidney Research UK The UK’s largest charity funding research into kidney disease.
• Kidney Care UK, the UK's leading kidney patient support charity | Kidney Care UK A UK based charity providing support to patients and families affected by kidney disease.
  
• National Kidney Federation UK based organisation which is an umbrella organisation for the regional kidney patient associations, providing support and guidance.
  
• Rare Kidney Disease Foundation Based in the USA but dedicated to ADTKD
  
• ADTKD Self-Help Rare Kidney Disease German organisation (Website also in English)

There is also an annual ADTKD international summit. Sessions are available to join online.