Clear cell renal cell carcinoma is the most common form of kidney cancer, affecting the tiny filtering tubes inside the kidneys. While it often grows without warning signs in the early stages, understanding this condition and the available treatment options can help patients and their families navigate the journey ahead with greater confidence.
Understanding Clear Cell Renal Cell Carcinoma
Clear cell renal cell carcinoma, often shortened to ccRCC, is a type of cancer that begins in the kidney. The name comes from how the cancer cells appear when doctors examine them under a microscope – they look clear and bubble-like, almost transparent. This happens because the cells contain fat and sugar molecules that wash away during laboratory preparation, leaving them with a distinctive clear appearance.[1]
This cancer starts in the cells lining the small tubes inside your kidneys called proximal tubules, which are responsible for filtering waste products from your blood. When these cells become cancerous, they multiply rapidly and form tumors. Most of the time, clear cell renal cell carcinoma affects only one kidney, though in rare cases both kidneys can be involved.[1]
Clear cell renal cell carcinoma belongs to a larger group of kidney cancers called renal cell carcinoma, or RCC. Within this group, the clear cell type is by far the most common, making up about 70 to 80 percent of all kidney cancer cases. In fact, kidney tumors in general account for more than 90 percent of all kidney cancers, and clear cell is the dominant subtype among them.[2][5]
How Common Is This Disease
In the United States, more than 81,000 people receive a kidney cancer diagnosis each year, according to the American Cancer Society. Among these cases, clear cell renal cell carcinoma represents the most frequently diagnosed type.[1] In adults, ccRCC accounts for approximately 80 percent of all renal cell carcinoma cases, making it a significant public health concern.[2]
The disease shows a clear pattern when it comes to who gets affected. Men are twice as likely to develop clear cell renal cell carcinoma compared to women. The condition typically appears in people between 50 and 70 years old, with the average age of diagnosis being 64 years.[1][6]
While clear cell renal cell carcinoma is predominantly a disease of adults, it can occur in children and young adults, though this is much less common. Renal cell carcinoma makes up only 2 to 6 percent of kidney cancer cases in childhood and young adults.[2]
The incidence of kidney cancer, including clear cell renal cell carcinoma, has been rising over recent decades. This increase may be partly due to improved imaging technology that allows doctors to detect kidney tumors earlier, often by accident when scanning for other medical conditions.[5]
What Causes Clear Cell Renal Cell Carcinoma
For most people who develop clear cell renal cell carcinoma, the exact cause remains unknown. Medical professionals and researchers have not identified a single clear reason why the cells in the kidney tubules begin to grow abnormally and form tumors.[1]
However, scientists have learned important information about the genetic changes involved in this cancer. Many cases of clear cell renal cell carcinoma involve changes in a gene called VHL, which stands for Von Hippel-Lindau. This gene normally helps control cell growth, but when it becomes damaged or mutated, cells can grow out of control. Interestingly, the VHL gene is altered not only in people who inherit a genetic condition but also in many people with ccRCC who have no family history of the disease.[2]
Understanding how the VHL gene works in the body has given scientists important clues about how to treat clear cell renal cell carcinoma. This knowledge has led to the development of targeted therapies that can interfere with the processes that allow cancer cells to grow and spread.[2]
Risk Factors That Increase Your Chances
While the direct cause of clear cell renal cell carcinoma is not known, researchers have identified several factors that can increase a person’s risk of developing this cancer. These are called risk factors, and some of them can be changed through lifestyle choices while others cannot.
Smoking and using tobacco products, including vaping, significantly increases the risk of developing clear cell renal cell carcinoma. The harmful chemicals in tobacco can damage the cells in your kidneys over time, making them more likely to become cancerous.[1][4]
Being overweight or having obesity is another major risk factor. When your body mass index, or BMI, is greater than 25, your risk increases. Research has shown that an increase in BMI of 5 kilograms per square meter, having central fat around your belly, and gaining weight between the ages of 18 and 35 have all been linked to a higher chance of developing kidney cancer.[3][4]
High blood pressure, also called hypertension, is another factor that raises your risk. The exact reason why high blood pressure increases kidney cancer risk is not completely understood, but it may be related to damage to the small blood vessels in the kidneys over time.[1][4]
People with chronic kidney disease who require dialysis face an increased risk of developing clear cell renal cell carcinoma. Dialysis is a treatment that filters waste from your blood when your kidneys can no longer do this job effectively. Similarly, people who have received a kidney transplant are at higher risk.[1][3]
Exposure to certain workplace toxins can increase risk. One example is trichloroethylene, a solvent used in some industrial settings. Workers who are regularly exposed to this chemical without proper protection may have a higher chance of developing kidney cancer.[1]
Long-term use of certain pain relievers, particularly acetaminophen (commonly sold as Tylenol), has been associated with an increased risk of clear cell renal cell carcinoma. However, this typically refers to prolonged use over many years, not occasional use for headaches or minor pain.[1]
Having diabetes mellitus alongside other conditions can also increase your risk. The relationship between diabetes and kidney cancer is complex and may be related to shared risk factors like obesity and high blood pressure.[3]
Inherited Genetic Conditions and Family History
While most cases of clear cell renal cell carcinoma occur sporadically without any family connection, the disease can run in families. If you have a biological sibling – a brother or sister who shares your parents – with renal cell carcinoma, you face a greater risk of developing the cancer yourself. Researchers are still working to understand exactly why this family connection exists.[1]
Some people inherit genetic conditions that make them much more likely to develop clear cell renal cell carcinoma. The most well-known of these conditions is Von Hippel-Lindau disease, or VHL disease. Almost all cases of ccRCC that run in families are found in people with this genetic syndrome.[2]
Von Hippel-Lindau disease is caused by mutations in the VHL gene. People with this condition develop cysts and tumors in different parts of their body. Most of these growths are not cancerous, but people with VHL disease have a much higher chance of developing clear cell renal cell carcinoma. When ccRCC does develop in these families, it often appears at a younger age than average.[1][2]
Other hereditary conditions beyond Von Hippel-Lindau syndrome may also be associated with clear cell renal cell carcinoma, though VHL disease is the most common genetic link. If you receive a diagnosis of ccRCC at a young age or if you have multiple tumors, your healthcare provider may recommend genetic testing to see if you have an inherited condition.[1][2]
Recognizing the Symptoms
One of the challenging aspects of clear cell renal cell carcinoma is that it usually does not cause any noticeable symptoms during the early stages of the disease. Many people with early kidney cancer feel perfectly fine and have no idea anything is wrong. This is why kidney tumors are often discovered accidentally when a doctor orders imaging tests for a completely different medical problem.[1][2]
However, as the condition progresses and the tumor grows larger, symptoms may begin to appear. One of the most common signs is blood in your urine, a condition called hematuria. You might notice that your urine looks pink, red, or cola-colored. Sometimes the amount of blood is so small that you cannot see it with your eyes, but it shows up when a doctor tests your urine.[1][2]
Feeling extremely tired, even when you get plenty of sleep, is another symptom that some people experience. This overwhelming tiredness is called fatigue, and it can interfere with your daily activities. It feels different from ordinary tiredness and does not get better with rest.[1][2]
Pain in your side or flank – the area between your ribs and hip on the side of your body where the affected kidney is located – can occur as the tumor grows. This pain might be dull and constant, or it might come and go. Some people describe it as a persistent ache.[1][2]
You might develop a fever without any obvious reason like an infection. This fever may come and go and does not respond to typical fever-reducing medications in the way that fever from an illness would.[1][2]
In some cases, you or your doctor might be able to feel a lump or mass in your side or abdomen. This happens when the tumor has grown large enough to be felt through the skin and muscle of your belly area.[1][2]
Losing weight without trying is another possible symptom. This unexplained weight loss can happen even when you are eating normally and not changing your diet or exercise habits.[1][2]
It is important to remember that these symptoms can also be caused by many other conditions, including noncancerous problems. Having one or more of these symptoms does not necessarily mean you have clear cell renal cell carcinoma. However, if you experience any of these signs, it is wise to talk to your doctor so they can determine what is causing them.[1]
Preventing Clear Cell Renal Cell Carcinoma
While there is no guaranteed way to prevent clear cell renal cell carcinoma, you can take steps to reduce your risk by addressing the modifiable risk factors – those aspects of your health and lifestyle that you have control over.
Quitting smoking and avoiding all tobacco products is one of the most important things you can do to lower your risk. If you currently smoke, talk to your doctor about smoking cessation programs and medications that can help you quit. Avoiding vaping and other tobacco products is equally important.[1]
Maintaining a healthy weight through balanced eating and regular physical activity can significantly reduce your risk. If you are overweight or have obesity, losing even a modest amount of weight can be beneficial. Focus on eating plenty of fruits, vegetables, and whole grains while limiting processed foods and unhealthy fats.[3]
Managing your blood pressure is another important preventive measure. If you have high blood pressure, work with your doctor to keep it under control through lifestyle changes and medication if needed. Regular monitoring and treatment of hypertension benefits not only your kidneys but your overall health.[1]
If you work with industrial chemicals or solvents, make sure you follow all workplace safety guidelines. Use protective equipment properly and ensure good ventilation in your work area to minimize exposure to potentially harmful substances like trichloroethylene.[1]
Be cautious about long-term use of pain relievers. While occasional use of over-the-counter pain medications like acetaminophen is generally safe, prolonged daily use over many years may increase risk. Talk to your doctor about pain management strategies if you need pain relief on a regular basis.[1]
For people with chronic kidney disease or diabetes, working closely with your healthcare team to manage these conditions may help reduce your overall risk. Regular check-ups and following your treatment plan are important for protecting your kidney health.[3]
If you have a family history of kidney cancer or a genetic condition like Von Hippel-Lindau disease, talk to your doctor about screening and monitoring options. While this does not prevent the cancer, it can help detect it at an earlier, more treatable stage.[1]
How the Disease Affects Your Body
Understanding what happens inside your body when you have clear cell renal cell carcinoma can help you make sense of your symptoms and treatment. This disease causes several important changes in how your kidneys and body normally function.
Your kidneys are bean-shaped organs about the size of your fist, located on either side of your spine in your lower back. Their main job is to filter your blood, removing waste products and excess water to create urine. Inside each kidney are millions of tiny filtering units that include the proximal tubules where clear cell renal cell carcinoma begins.[1][2]
When cancer develops in the cells lining these tubules, the cells begin to multiply rapidly and abnormally. Unlike normal cells, which grow in an orderly way and die when they become old or damaged, cancer cells keep dividing and do not die when they should. This uncontrolled growth creates a mass of tissue called a tumor.[1]
The cancer cells in clear cell renal cell carcinoma look distinctive under a microscope because they appear clear and bubbly. This happens because these cells accumulate lipids (fats) and glycogen (a form of stored sugar) in their cytoplasm. When pathologists prepare tissue samples for examination, these substances wash away, leaving the cells looking clear or empty.[5]
As the tumor grows, it can interfere with kidney function. The cancer may damage the normal kidney tissue around it, reducing the kidney’s ability to filter blood effectively. If the tumor becomes large enough, it can cause the kidney to work less efficiently or even stop working altogether in severe cases.[1]
Clear cell renal cell carcinoma has a tendency to spread through the bloodstream rather than primarily through the lymphatic system, though it can use both routes. The cancer cells can invade nearby blood vessels, including the renal vein (the main vein draining the kidney) and even extend into the inferior vena cava, which is the large vein that carries blood back to your heart. This direct extension into major blood vessels is one of the characteristic features of this type of cancer.[3][5]
When clear cell renal cell carcinoma spreads beyond the kidney to other parts of the body – a process called metastasis – it most commonly travels to the lungs, bones, lymph nodes, liver, and brain. The cancer cells can also spread to the adrenal glands, which sit on top of each kidney. When the cancer reaches the bones, it typically causes lytic lesions, which means the cancer eats away at the bone tissue, though these lesions may become denser or sclerotic with treatment.[3][5]
One unusual feature of clear cell renal cell carcinoma is that it can sometimes cause symptoms that seem unrelated to the kidneys. These are called paraneoplastic manifestations or paraneoplastic syndromes. The cancer cells may produce hormones or other substances that affect other parts of your body, leading to symptoms like high calcium levels in the blood, increased red blood cell production, or liver function abnormalities even when the cancer has not spread to these organs.[3]
The cancer can grow at different rates in different people. Some tumors grow slowly over months or years, while others are more aggressive and spread quickly. Even after initial treatment, clear cell renal cell carcinoma can recur, sometimes many years later. Late recurrence is one of the characteristics of this disease, which is why long-term follow-up with your doctor is so important.[3]
If the affected kidney is removed or stops functioning due to cancer, your remaining kidney usually takes over the work of filtering your blood. One healthy kidney can typically do the job of two, though you may need to make some adjustments to protect that remaining kidney. If both kidneys are affected or if your remaining kidney is not healthy, you may eventually need dialysis or a kidney transplant.[1]
