Tuberous Sclerosis Complex (TSC) is a genetic disorder causing non-cancerous tumors to develop in many parts of the body. It results from mutations in the TSC1 or TSC2 gene, leading to overactivation of a cellular growth pathway. While growths can appear in the brain, skin, heart, and lungs, the kidneys are one of the most affected organs.
Approximately 80% of individuals with TSC develop kidney issues, which often start in childhood and progress over time. These complications can affect kidney function and may lead to serious health problems if not properly monitored. About half of those with kidney involvement will require some form of treatment by age 40.
Kidney Complications in Tuberous Sclerosis
The most common kidney complication in TSC is the growth of tumors called angiomyolipomas (AMLs). These benign growths are composed of abnormal blood vessels, muscle cells, and fat tissue. AMLs are found in about 80% of adults with TSC, can be present in both kidneys, and pose a risk as they grow larger.
The primary danger of AMLs is that their poorly formed blood vessels can weaken and form an aneurysm, which may rupture. A rupture can cause severe internal bleeding (hemorrhage) into the abdomen, leading to pain, blood in the urine, and shock. The likelihood of a bleeding event increases as AMLs grow, particularly when they exceed 4 centimeters in diameter.
Individuals with TSC may also develop renal cysts, which are fluid-filled sacs on the kidneys. About one-quarter of people with TSC have renal cysts, which cause fewer direct problems than AMLs but still require observation. In some cases, a high number of cysts, a condition known as polycystic kidneys, requires more specialized monitoring.
A less common complication is an elevated risk for developing renal cell carcinoma (RCC), a type of kidney cancer. The estimated risk is between one and four percent, but it can occur at a younger age in the TSC population. These cancers are often slow-growing and can be difficult to distinguish from AMLs with a low-fat composition.
Diagnosis and Regular Monitoring
Diagnosing and tracking kidney lesions in TSC relies on imaging. An abdominal ultrasound is often used for initial screening, but computed tomography (CT) or magnetic resonance imaging (MRI) scans provide more detail. MRI is the preferred method, especially for children, as it avoids radiation and clearly shows the size, number, and composition of AMLs and cysts.
These detailed images are important for planning treatments. They help doctors assess features like the fat content of an AML, which helps differentiate it from renal cell carcinoma. The scans also allow for identifying aneurysms within the tumors, a factor in assessing bleeding risk.
Lifelong surveillance is standard practice. After a baseline scan at diagnosis, individuals undergo routine monitoring every one to three years. The frequency of follow-up scans depends on the size and growth rate of existing lesions, allowing healthcare providers to recommend treatment at the appropriate time.
Treatment for Kidney Lesions
Medical therapy is often the first line of defense for kidney lesions in TSC. Medications known as mTOR inhibitors, such as everolimus, target the overactive cellular pathway that drives tumor growth. These drugs can effectively shrink existing angiomyolipomas and help prevent new ones from forming. This treatment is useful for individuals with large or growing AMLs who do not require immediate surgery.
For large AMLs, those with a high risk of bleeding, or those actively bleeding, selective arterial embolization is a common intervention. In this minimally invasive procedure, an interventional radiologist guides a catheter to the artery supplying the AML. Tiny particles are then injected to block blood flow to the tumor, causing it to shrink and reducing the risk of rupture.
Surgical options are reserved for complex situations, such as for very large tumors or when bleeding cannot be controlled with embolization. The goal of surgery is to preserve as much healthy kidney tissue as possible. A partial nephrectomy, where only the tumor is removed, is preferred over a total nephrectomy, which removes the entire kidney and is only considered in extreme cases.
Long-Term Kidney Function Management
Managing long-term kidney health is an important part of TSC care. A common issue is hypertension (high blood pressure), which can strain the kidneys and accelerate function loss. Controlling blood pressure is a priority, often with medications like ACE inhibitors and regular monitoring.
In addition to imaging, regular blood and urine tests monitor kidney performance. Blood tests measure creatinine to estimate the glomerular filtration rate (GFR), which indicates how well the kidneys are working. Urine tests check for protein, a potential sign of kidney damage.
The cumulative impact of AMLs, cysts, and their treatments can lead to chronic kidney disease (CKD). While the risk of complete kidney failure requiring dialysis or a transplant is low (about 1-4%), the risk of developing some level of CKD is higher than in the general population. This highlights the need for proactive management to protect kidney function.