kidney cancer: Symptoms, Causes, Prevention and Treatment

Kidney cancer also called renal cancer -- is a disease in which kidney cells become malignant (cancerous) and grow out of control, forming a tumor.

The kidneys are a pair of bean-shaped organs, each about the size of a fist. They are attached to the upper back wall of the abdomen and protected by the lower rib cage. One kidney is just to the left and the other just to the right of the backbone.

Types of kidney cancer

Renal cell carcinoma

Renal cell carcinoma (RCC), also known as renal cell cancer or renal cell adenocarcinoma, is by far the most common type of kidney cancer. About 9 out of 10 kidney cancers are renal cell carcinomas.

Although RCC usually grows as a single tumor within a kidney, sometimes there are 2 or more tumors in one kidney or even tumors in both kidneys at the same time.

There are several subtypes of RCC, based mainly on how the cancer cells look under a microscope. Knowing the subtype of RCC can be a factor in deciding treatment and can also help your doctor determine if your cancer might be due to an inherited genetic syndrome. See  What Are the Risk Factors for Kidney Cancer? for more information about inherited kidney cancer syndromes.

Clear cell renal cell carcinoma: this is the most common form of renal cell carcinoma. About 7 out of 10 people with RCC have this kind of cancer. When seen under a microscope, the cells that make up clear cell RCC look very pale or clear.

• Papillary renal cell carcinoma: this is the second most common subtype – about 1 in 10 RCCs are of this type. These cancers form little finger-like projections (called papillae) in some, if not most, of the tumor. Some doctors call these cancers chromophilic because the cells take in certain dyes and look pink under the microscope.

• Chromophobe renal cell carcinoma: this subtype accounts for about 5% (5 cases in 100) of RCCs. The cells of these cancers are also pale, like the clear cells, but are much larger and have certain other features that can be recognized when looked at with a microscope .

Rare types of renal cell carcinoma: these subtypes are very rare, each making up less than 1% of RCCs:

• Collecting duct RCC
• Multilocular cystic RCC
• Medullary carcinoma
• Mucinous tubular and spindle cell carcinoma
• Neuroblastoma-associated RCC
• Unclassified renal cell carcinoma: rarely, renal cell cancers are labeled as unclassified because the way they look doesn’t fit into any of the other categories or because there is more than one type of cell present.

Other types of kidney cancers

Other types of kidney cancers include transitional cell carcinomas, Wilms tumors, and renal sarcomas.

• Transitional cell carcinoma: of every 100 cancers in the kidney, about 5 to 10 are transitional cell carcinomas (TCCs), also known as urothelial carcinomas.

Transitional cell carcinomas don’t start in the kidney itself, but in the lining of the renal pelvis (where the ureters meet the kidneys). This lining is made up of cells called transitional cells that look like the cells that line the ureters and bladder. Cancers that develop from these cells look like other urothelial carcinomas, such as bladder cancer, under the microscope. Like bladder cancer, these cancers are often linked to cigarette smoking and being exposed to certain cancer-causing chemicals in the workplace.

People with TCC often have the same signs and symptoms as people with renal cell cancer − blood in the urine and, sometimes, back pain.

• Wilms tumor (nephroblastoma): Wilms tumors almost always occur in children. This type of cancer is very rare among adults. To learn more about this type of cancer, see Wilms Tumor.

• Renal sarcoma: renal sarcomas are a rare type of kidney cancer that begin in the blood vessels or connective tissue of the kidney. They make up less than 1% of all kidney cancers.

Risk Factors for Kidney Cancer

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like your age or family history, can’t be changed.

But having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors. Even if a person with kidney cancer has a risk factor, it is often very hard to know how much that risk factor contributed to the cancer.

Scientists have found several risk factors that could make you more likely to develop kidney cancer.

Smoking

Smoking increases the risk of developing renal cell carcinoma (RCC). The increased risk seems to be related to how much you smoke. The risk drops if you stop smoking, but it takes many years to get to the risk level of someone who never smoked.

Obesity

People who are very overweight have a higher risk of developing RCC. Obesity may cause changes in certain hormones that can lead to RCC.

Workplace exposures

Many studies have suggested that workplace exposure to certain substances increases the risk for RCC. Some of these substances are cadmium (a type of metal), some herbicides, and organic solvents, particularly trichloroethylene.

Family history of kidney cancer

People with a strong family history of renal cell cancer (without one of the known inherited conditions listed below) have a higher chance of developing this cancer. This risk is highest for people who have a brother or sister with the cancer. It’s not clear whether this is due to shared genes, something that both people were exposed to in the environment, or both.

High blood pressure

The risk of kidney cancer is higher in people with high blood pressure. Some studies have suggested that certain medicines used to treat high blood pressure may raise the risk of kidney cancer, but it is hard to tell if it’s the condition or the medicine (or both) that may be the cause of the increased risk.

Certain medicines

Phenacetin: This drug used to be a popular non-prescription pain reliever and has been linked to RCC in the past. But it has not been available in the United States for over 30 years, so it no longer appears to be a major risk factor.

Diuretics: Some studies have suggested that diuretics (water pills) may be linked to a small increase in the risk of RCC. It is not clear whether the cause is the drugs or the high blood pressure they treat. If you need to take diuretics, don’t avoid them to try to reduce the risk of kidney cancer.

Advanced kidney disease

People with advanced kidney disease, especially those needing dialysis, have a higher risk of RCC. Dialysis is a treatment used to remove toxins from your body if the kidneys do not work properly.

Gender

RCC is about twice as common in men as in women. Men are more likely to be smokers and are more likely to be exposed to cancer-causing chemicals at work, which may account for some of the difference.

Race

African Americans and American Indians/Alaska Natives have slightly higher rates of RCC than do whites. The reasons for this are not clear.

Genetic and hereditary risk factors

Some people inherit a tendency to develop certain types of cancer. The DNA in each of your cells that you get from your parents may have changes that give you this tendency. Some rare inherited conditions can cause kidney cancer. It is important that people who have hereditary causes of RCC see their doctors often, especially if they have already been diagnosed with RCC. Some doctors recommend regular imaging tests (such as CT scans) to look for new kidney tumors in these people.

People who have the conditions listed here have a much higher risk for getting kidney cancer, although they account for only a small portion of cases overall.

von Hippel-Lindau disease

People with this condition often develop several kinds of tumors and cysts (fluid-filled sacs) in different parts of the body. They have an increased risk for developing clear cell RCC, especially at a younger age. They may also have benign tumors in their eyes, brain, spinal cord, pancreas, and other organs; and a type of adrenal gland tumor called pheochromocytoma. This condition is caused by mutations (changes) in the VHL gene.

Hereditary papillary renal cell carcinoma

People with this condition have a tendency to develop one or more papillary RCCs, but they do not have tumors in other parts of the body, as is the case with the other inherited conditions listed here. This disorder is usually linked to changes in the MET gene.

Hereditary leiomyoma-renal cell carcinoma

People with this syndrome develop smooth muscle tumors called leiomyomas (fibroids) of the skin and uterus (in women) and have a higher risk for developing papillary RCCs. It has been linked to changes in the FH gene.

Birt-Hogg-Dube (BHD) syndrome

People with this syndrome develop many small benign skin tumors and have an increased risk of different kinds of kidney tumors, including RCCs and oncocytomas. They may also have benign or malignant tumors of several other tissues. The gene linked to BHD is known as FLCN.

Familial renal cancer

People with this condition develop tumors called paragangliomas of the head and neck region, as well as tumors known as pheochromocytomas of the adrenal glands and thyroid cancers. They also tend to get kidney cancer in both kidneys before age 40. It is caused by defects in the genes SDHB and SDHD.

Cowden syndrome

People with this syndrome have a high risk of breast, thyroid and kidney cancers. It is linked to changes in the  PTEN gene.

Tuberous sclerosis

People with this syndrome develop many, usually benign (noncancerous) tumors in different parts of the body including the skin, brain, lungs, eyes, kidneys, and heart. Although the kidney tumors are most often benign, occasionally they can be clear cell RCC. It is caused by defects in the genes TSC1 and TSC2.

Hereditary renal oncocytoma

Some people inherit the tendency to develop a kidney tumor called an oncocytoma, which is almost always benign (not cancer).

What Causes Kidney Cancer?

Although many risk factors can increase the chance of developing renal cell cancer (RCC), it is not yet clear how some of these risk factors cause kidney cells to become cancerous.

Changes (mutations) in genes

Cancer is caused by changes in the DNA inside our cells. DNA is the chemical in our cells that makes up our genes, which control how our cells function. DNA, which comes from both our parents, affects more than just how we look.

Some genes help control when our cells grow, divide into new cells, and die:

Certain genes that help cells grow, divide, and stay alive are called oncogenes.
Genes that help keep cell division under control or cause cells to die at the right time are called tumor suppressor genes.
Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes, resulting in cells growing out of control. Changes in many different genes are usually needed to cause kidney cancer.

Inherited gene mutations

Certain inherited DNA changes can lead to conditions running in some families that increase the risk of kidney cancer. These syndromes, which cause a small portion of all kidney cancers, were described in What Are the Risk Factors for Kidney Cancer?

For example, VHL, the gene that causes von Hippel-Lindau (VHL) disease, is a tumor suppressor gene. It normally helps keep cells from growing out of control. Mutations (changes) in this gene can be inherited from parents. When the VHL gene is mutated, it is no longer able to control the abnormal growth, and kidney cancer is more likely to develop. The genes linked to hereditary leiomyoma  (the FH gene), Birt-Hogg-Dube syndrome (the FLCN gene), and familial renal cancer (the SDHB and SDHD genes) are also tumor suppressor genes, and inherited changes in these genes lead to an increased risk of kidney cancer.

People with hereditary papillary renal cell carcinoma have inherited changes in the MET oncogene that cause it to be turned on all the time. This can lead to uncontrolled cell growth and makes the person more likely to develop papillary RCC.

Special genetic tests can detect some of the gene mutations associated with these inherited syndromes. If you have a family history of kidney cancer or other cancers linked to these syndromes, you may want to ask your doctor about genetic counseling and genetic testing. The American Cancer Society recommends discussing genetic testing with a qualified cancer genetics professional before any genetic testing is done. For more on this, see Understanding Genetic Testing for Cancer and What Happens during Genetic Testing for Cancer? 

Acquired gene mutations

Some gene mutations happen during a person’s lifetime and are not passed on. They affect only cells that come from the original mutated cell. These DNA changes are due to acquired mutations.

In most cases of kidney cancer, the DNA mutations that lead to cancer are acquired during a person’s life rather than having been inherited. Certain risk factors, such as exposure to cancer-causing chemicals (like those found in tobacco smoke), probably play a role in causing these acquired mutations, but so far it’s not known what causes most of them. Progress has been made in understanding how tobacco increases the risk for developing kidney cancer. Your lungs absorb many of the cancer-causing chemicals in tobacco smoke into the bloodstream. Because your kidneys filter this blood, many of these chemicals become concentrated in the kidneys. Several of these chemicals are known to damage kidney cells in ways that can cause the cells to become cancerous.

Obesity, another risk factor for this cancer, alters the balance of some of the body’s hormones. Researchers are now learning how certain hormones help control the growth (both normal and abnormal) of many different tissues in the body, including the kidneys.

Most people with sporadic (non-inherited) clear cell RCC have changes in the VHL gene in their tumor cells that have caused it to stop working properly. These changes are acquired during life rather than being inherited.

Other gene changes may also cause renal cell carcinomas. Researchers continue to look for these changes. For more about how genes changes can lead to cancer, see Genes and Cancer.

How is renal cell carcinoma diagnosed?
If your doctor suspects that you may have RCC, they’ll ask about your personal and family medical history. They’ll then do a physical exam. Findings that can indicate RCC include swelling or lumps in the abdomen, or, in men, enlarged veins in the scrotal sac (varicocele).

If RCC is suspected, your doctor will order a number of tests to get an accurate diagnosis. These may include:

complete blood count — a blood test conducted by drawing blood from your arm and sending it to a lab for evaluation
CT scan — an imaging test that allows your doctor to take a closer look at your kidneys to detect any abnormal growth
abdominal and kidney ultrasounds — a test that uses sound waves to create a picture of your organs, allowing your doctor to look for tumors and problems within the abdomen
urine examination — tests used to detect blood in the urine and to analyze cells in the urine looking for evidence of cancer
biopsy — the removal of a small piece of kidney tissue, done by inserting a needle into the tumor and drawing out a tissue sample, which is then sent to a pathology lab to rule out or confirm the presence of cancer
If you are found to have RCC, more tests will be done to find out if and where the cancer has spread. This is called staging. RCC is staged from stage 1 to stage 4, in order of ascending severity. Staging tests can include a bone scan, PET scan, and chest X-ray.

Approximately one-third of individuals with RCC have cancer that has spread at the time of diagnosis.

Treatments for renal cell carcinoma
There are five kinds of standard treatments for RCC. One or more may be used to treat your cancer.

Surgery can include different types of procedures. During a partial nephrectomy, part of the kidney is removed. During a nephrectomy, the entire kidney may be removed. Depending on how far the disease has spread, more extensive surgery may be needed to remove surrounding tissue, lymph nodes, and your adrenal gland. This is a radical nephrectomy. If both kidneys are removed, dialysis or a transplant is necessary.
Radiation therapy involves using high-energy X-rays to kill cancer cells. The radiation can be given externally by a machine or placed internally using seeds or wires.
Chemotherapy uses drugs to kill cancer cells. It can be given orally or intravenously, depending on what medication is chosen. This allows the drugs to go through the bloodstream and reach cancer cells that may have spread to other parts of the body.
Biologic therapy, also called immunotherapy, works with your immune system to attack the cancer. Enzymes or substances made by the body are used to defend your body against the cancer.
Targeted therapy is a newer kind of cancer therapy. Drugs are used to attack certain cancer cells without damaging healthy cells. Some drugs work on blood vessels to prevent blood flow to the tumor, “starving” and shrinking it.

Prevention

Taking steps to improve your health may help reduce your risk of kidney cancer. To reduce your risk, try to:

Quit smoking. If you smoke, quit. Many options for quitting exist, including support programs, medications and nicotine replacement products. Tell your doctor you want to quit, and discuss your options together.
Maintain a healthy weight. Work to maintain a healthy weight. If you're overweight or obese, reduce the number of calories you consume each day and try to be physically active most days of the week. Ask your doctor about other healthy strategies to help you lose weight.
Control high blood pressure. Ask your doctor to check your blood pressure at your next appointment. If your blood pressure is high, you can discuss options for lowering your numbers. Lifestyle measures such as exercise, weight loss and diet changes can help. Some people may need to add medications to lower their blood pressure. Discuss your options with your doctor.