Many people with tuberous sclerosis complex (TSC) will develop some signs of TSC 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.
- Lifelong surveillance is vital to tracking TSC growths in the kidneys and being able to offer treatment at the right time.
- New medicine for TSC kidneys has been approved and TSC experts recommend early identification and treatment of kidney 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.
Doctors who specialise in kidneys are called nephrologists. Another term used by health professionals for things to do with the kidneys is ‘renal’ and kidney doctors are also called renal physicians. Surgeons who operate on kidneys are called urologists. Nephrectomy is the term given for the partial or full removal of a kidney.
Signs and Symptoms
Kidneys can be affected by TSC in a number of ways.
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. More research into AMLs is required to understand more about the risk of bleeding however it is generally agreed that bleeding is very unlikely if an AML is less than 4cm in size. This is why surveillance is so important.
Cysts in the kidneys are generally small and do not cause symptoms for most people with TSC. Cysts can be seen on an ultrasound.
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 excess growth of kidney epithelial cells, which form the lining of the cysts.
Up to five percent of people with TSC will also have autosomal dominant polycystic kidney disease. The gene for polycystic kidney disease is right next to the TSC2 gene. People with both diseases have a large deletion 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.
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.
Chronic kidney disease (CKD) occurs when a person’s kidneys are no longer able 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 of AMLs: the risk of CKD increases if the person with TSC has larger 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.
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.
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
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.
- Measure blood pressure and glomerular filtration rate to understand kidney function.
For individuals already diagnosed with TSC
- Obtain abdominal MRI every 1-3 years to monitor renal and non-renal TSC disease progression.
- Check blood pressure and glomerular filtration rate at least annually.
The recommendation for MRIs can be difficult to follow in Australia because MRIs are not funded in our public health system. Many people with TSC in Australia have regular kidney ultrasounds, in place of MRIs, to monitor their kidneys.
A kidney ultrasound may also be recommended by your doctor because a general anaesthetic would be required or because MRI is contra-indicated for a particular individual. However, abdominal MRIs may provide more information than ultrasounds and are particularly useful if AMLs are fat-poor.
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 possibly increase their risk of cancer later in life. 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.
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. These symptoms should be shared with carers of people with AMLs who may have trouble communicating the pain they feel.
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.
1. 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.
2. Treatment for a large and growing AML
mTOR inhibitor medicines are recommended to treat AMLs that are larger than three 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.
Prepared by: Clare Stuart, Tuberous Sclerosis Australia
Reviewed by: Dr Sean Kennedy, Paediatric Nephrologist, Sydney Children’s Hospital and Dr Nikky Isbel, Nephrologist, Princess Alexandra Hospital in Brisbane.
- Kwiatkowski D.J., Whittemore V.H. & Thiele E.A. (2010) Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Weinheim: Wiley-Blackwell
- Tuberous Sclerosis Association (United Kingdom). Factsheet on TSC and Kidneys. Viewed 7 August 2017.
- Tuberous Sclerosis Alliance, Kidneys, viewed 7 August 2017
- Kingswood J, C, Bissler J, J, Budde K, Hulbert J, Guay-Woodford L, Sampson J, R, Sauter M, Cox J, Patel U, Elmslie F, Anderson C, Zonnenberg B, A, Review of the Tuberous Sclerosis Renal Guidelines from the 2012 Consensus Conference: Current Data and Future Study. Nephron 2016;134:51-58