kidneys130

Kidneys

50164998891 683c303537 o 1

Many people with TSC will develop some signs of TSC (Tuberous Sclerosis Complex) in their kidneys during their lifetime.

However, with proper surveillance and care, most people with TSC can avoid major kidney problems. Sometimes kidney disease can be the first clue that a person has TSC; in other people it might first be detected in adulthood.

The most important things to know about TSC and the kidneys are:

  • Lifelong surveillance is vital to tracking TSC growths in the kidneys and being able to offer treatment at the right time.
  • A medicine to treat TSC kidneys is available and TSC experts recommend early identification and treatment of kidney growths called angiomyolipomas (AMLs).
  • Kidneys should only be removed in very extreme cases, and this should be avoided, if possible.
  • The risk of kidney cancer in TSC is sometimes overstated and a TSC expert should be consulted before cancer treatment is considered.

Here is a glossary of medical terms associated with the kidneys:

Kidney – the organ responsible for filtering the blood and producing urine
Renal – a term used to refer to kidney related things
Nephrologist – a doctor who specialises in kidney medicine
Renal Physician – another word for a kidney doctor
Urologist – a surgeon who operates on kidneys
Angiomyolipoma (AML) – a non-cancerous tumour made up of blood vessels, muscle cells and fat cells
Nephrectomy – an operation to remove all or part of the kidney
Embolisation – a procedure to block off the local blood supply to a tumour or tissue in the body.

You might want to watch this useful explanatory video interview with Dr Sean Kennedy. Adults living with TSC may also want to refer to this video by Dr Matt Sypek.

Signs, Symptoms and
Treatments

Brain
Epilepsy
Eyes
Heart
Kidneys
Lungs
mTOR Inhibitors
Skin
TAND

Signs and Symptoms

Kidneys can be affected by TSC in a number of ways.

kidneys130
Angiomyolipomas (AMLs)

AMLs are benign tumours in the kidneys which are made up of blood vessels (angio), muscle (myo) and fat (lipo). The presence of fat in AMLs allows them to be distinguished from other kidney tumours by magnetic resonance imaging (MRI), computerised axial tomography (CT) scan or ultrasound imaging.

Researchers estimate that approximately 80 percent of people with TSC will develop AMLs during their lifetime. Although most people with TSC will develop AMLs, most people with TSC and AMLs won’t have major problems.

Kidney AMLs can cause concern if they start to bleed. Bleeding is rare but can be severe. A bleeding AML may cause back or abdominal pain or blood to be seen in the urine. In severe cases, AMLs can result in haemorrhage and shock and need urgent therapy, usually with embolisation. Embolisation involves a procedure that blocks off the bleeding vessel. Bleeding is very unlikely if an AML is less than 4cm in size. The risk of bleeding increases as the size of the AML increases and if the tumour contains abnormal dilated blood vessels.

Different treatments are available for AML, including a medication that can reduce the size of the tumours. The need for treatment can depend on the number of AMLs, their size, how quickly they are growing and other factors. This is why surveillance scans and follow up with a TSC expert is so important.

Kidney cysts

A cyst is a pocket of fluid detected inside an organ of the body. They can be seen on ultrasound or other medical scans and look a bit like a bubble full of fluid. For most people with TSC, kidney cysts are generally small and do not cause symptoms or other problems.

Exactly how kidney cysts develop is not known. The TSC genes are believed to produce tumour suppressor proteins. Normally, tumour suppressor proteins prevent excess cell growth. When the TSC genes are inactivated by gene mutations, these tumour suppressor proteins are not produced and cell growth is unchecked. Cysts may, therefore, be the result of an excess of the cells lining the drainage tubes of the kidney, known as epithelial cells.

Polycystic kidney disease

Up to five percent of people with TSC will also have a condition called autosomal dominant polycystic kidney disease (ADPKD) in which cysts on the kidneys can grow very large and start to affect how the kidneys work. The gene for polycystic kidney disease is on a chromosome right next to the TSC2 gene. People with both diseases have a large piece of their DNA missing that goes across both of these adjacent genes. For these people, their severe polycystic kidney disease will usually be visible during childhood or even before birth. As the cysts grow very large they can start to affect kidney function and may lead to high blood pressure and kidney failure.

Kidney Cancer

People with TSC may have an increased risk of developing kidney cancer (renal cell carcinoma or RCC). The risk has been estimated to be between one and four percent and can occur at a younger age than in the general population.

These cancers are usually slow growing. If they are found early, they can be removed from the kidney, preserving kidney function. This is another reason why surveillance is important. It may be difficult to distinguish cancers from AMLs, particularly when the AMLs do not have much fat in them. Sometimes a CT scan, MRI or biopsy will be required. This can be an important time to seek the advice of the multidisciplinary team or a renal physician who is very familiar with TSC.

For a person with TSC, it is much more likely that they will develop AMLs than it is that they will develop kidney cancer.

Impaired kidney function

Most people with TSC will have normal kidney function.

Chronic kidney disease (CKD) occurs when a person’s kidneys have reduced ability to perform the functions of clearing the waste products and excess fluid from the body. The kidneys have a lot of reserve capacity and some people may have a decrease in level of function but no symptoms. The risk of a person with TSC developing CKD increases with these risk factors:

  • Age: the risk of CKD increases as a person with TSC gets older
  • Size and number of AMLs: the risk of CKD increases if the person with TSC has larger or multiple AMLs
  • Previous surgery to remove part of the kidney: the risk of CKD increases if previous sections of the kidney have been removed with surgery.
  • Presence of Autosomal Dominant Polycystic Kidney Disease: the risk of CKD is much higher in people who have both TSC2 and PKD1 genes missing
  • Presence of other risk factors for CKD: just like people without TSC, diabetes, high blood pressure and smoking increase the risk of CKD

Only some people with TSC experience some degree of kidney impairment. Kidney failure occurs rarely in TSC except for people who also have severe polycystic kidney disease. If kidney failure occurs then dialysis or a kidney transplant are possible. A kidney transplant will not be affected by TSC.

Regular surveillance and early treatment are the best tools to reduce the risk of a person with TSC experiencing impaired kidney function.

Surveillance and Prevention

36047350474 161676e324 o 1

Surveillance is important because it can lead to early detection and treatment. Each person with TSC should have an individual management plan developed with their medical team that uses these guidelines as a starting point.

For people newly diagnosed with TSC or when TSC is suspected:

  • Perform magnetic resonance imaging (MRI) of the abdomen to check for possible renal angiomyolipomas or cysts.
  • Test for high blood pressure
  • Have a blood test to check kidney function
  • Have a urine test for blood and protein.

For individuals already diagnosed with TSC:

  • Obtain abdominal MRI every 1-3 years to monitor renal and non-renal TSC disease progression (see note below re more common use of ultrasound/imaging in Australia).
  • Check blood pressure, kidney function (glomerular filtration rate) and screen for increased levels of protein in the urine at least annually.

Source: Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management: Recommendations 2021

Note: Although the international guidelines reference MRI of the abdomen, historically in Australia, an ultrasound or CT scan of the kidneys was sometimes used in place of an MRI as abdominal MRIs were not funded under the medical benefits scheme (MBS). However, thanks to the work of TSA and others, abdominal MRIs are being funded under the medical benefits scheme (MBS) from 1 July 2024. Abdominal MRIs may be particularly useful if AMLs are fat-poor.

It is important that a person can lie still for an MRI scan. For people with TSC who have an intellectual disability or are very young, a general anaesthetic may be required before an MRI scan can be done. In these cases it is recommended to combine imaging so that multiple tests can be performed. Some people with TSC combine: abdominal MRI, brain MRI, blood tests, dental procedures and more. Although this can be very difficult to organise, people with TSC and their families find this approach minimises the impact of these tests on their lives as well as reducing risks of anaesthetic.

CT is not recommended for regular surveillance for people with TSC due to risks associated with the radiation that CT scans use. This is because people with TSC will require imaging throughout their life and repeated CT scans will lead to increased exposure to radiation. However, MRI is not useful for detecting lung disease so women with TSC will have CT scans performed. Read more in our information page about TSC and the lungs.

Monitoring blood pressure is important because high blood pressure, or hypertension, can accelerate a loss of kidney function. Blood tests to measure glomerular filtration rate find out how well the kidneys are working.

People with TSC should aim for a healthy diet and lifestyle to ease the burden on the kidneys and avoid high blood pressure. Kidney Health Australia has more information about keeping kidneys healthy.

Read more about keeping your kidneys healthy.

Although it is written for people with chronic kidney disease it is useful for all people with TSC because of the risk of developing kidney disease associated with TSC.

People with AMLs should be aware of the type of symptoms that are associated with bleeding from AMLs. This includes back or abdominal pain, nausea, vomiting, high temperature and dark or blood stained urine. A major bleed from an AML can also present with sudden dizziness, fast heart rate, low blood pressure or collapse. These symptoms should be shared with carers of people with AMLs.

Treatment

Many people with TSC will not require any treatment for their kidneys. Kidney cysts and small AMLs do not require treatment.

High blood pressure should be treated to reduce the stress on the kidneys. Polycystic kidney disease and chronic kidney disease should be treated as they are for the non-TSC population.

Angiomyolipomas (AMLs) should be treated if they bleed or if they are large and/or growing.

Treatment for a bleeding AML

Embolisation is a procedure that blocks the blood vessels that supply the AMLs. This stops the bleeding and causes the AML to shrink. It is very important that this is combined with corticosteroids for seven days to reduce the risk of post-embolisation syndrome.

Treatment for a large and growing AML

A group of medications called mTOR inhibitors are recommended to treat AMLs in people with TSC that are larger than 3 centimetres in diameter and continue to grow. The medicine approved in Australia for this purpose is Everolimus (Afinitor) and it is available on the Pharmaceutical Benefits Scheme (PBS). You should discuss this medicine with your doctor if you have an AML that is 3cm or larger in size. Your doctor can consider your personal circumstances including age, growth rate and other aspects of your health to make a decision about whether this medicine is a suitable treatment. You can read more about this medicine on our mTOR inhibitors information page.

This medicine is known to reduce the size of AMLs and we know that smaller AMLs have a lower risk of bleeding. We don’t yet know whether treatment with mTOR inhibitors reduces the risk of a person with TSC developing chronic kidney disease. More research is being done to understand their role in keeping TSC kidneys healthier for longer.

Alternative treatment options for AMLs include embolisation and surgery. Surgery should aim to preserve as much kidney tissue as possible and partial and full nephrectomy should be avoided. While there are some people with TSC who have had successful kidney transplants, the aim of regular surveillance and appropriate intervention is to keep the kidney as healthy as possible.

Treatment of chronic kidney disease

People with TSC and impaired kidney function should talk to their doctor about treatments to help prevent further decline in their kidneys. These treatments include managing other risk factors for kidney disease such as increased blood pressure, high cholesterol and diabetes. Medications are also available that help to slow the decline in kidney function for people with established kidney disease and increased urine protein levels.

Last updated: 25 October 2022

Reviewed by: Dr Nikky Isbel, Nephrologist, Princess Alexandra Hospital in Brisbane, Dr Sean Kennedy, Paediatric Nephrologist, Sydney Children’s Hospital, Dr Matthew Sypek, Nephrologist, Royal Children’s Hospital Melbourne and Royal Melbourne Hospital