Clear cell carcinoma of the kidney is a cancer that starts in the tiny tubules of the kidney that filter blood and make urine. Doctors also call it clear cell renal cell carcinoma. The cells look pale or “clear” under the microscope because fat and sugar are washed out during tissue processing. This type is the most common kidney cancer in adults and makes up about 70–80% of all renal cell cancers. It usually starts in the proximal tubule, a small tube inside the kidney.
Clear cell carcinoma of the kidney (clear cell renal cell carcinoma, ccRCC) is the most common type of kidney cancer in adults. It starts from the tiny filtering units of the kidney (proximal tubules). Under the microscope the cancer cells look “clear” because they are full of fat and sugar. It can stay only in the kidney or spread to lymph nodes, lungs, bones, liver, or brain. Modern treatment uses surgery, targeted pills, and immune-based medicines, often in combination, depending on the stage and risk group.
Clear cell kidney cancer is strongly linked with changes in genes that control blood vessel growth, especially the VHL gene. These changes make the tumor create many abnormal blood vessels and signals such as VEGF, which help it grow and spread. Because of this, many key drugs for ccRCC block VEGF or related pathways, or “wake up” the immune system so it can attack the cancer more effectively.
In clear cell carcinoma, important genes that normally protect the cell from becoming cancer, such as the VHL gene on chromosome 3p, are often damaged or switched off. When the VHL gene does not work, hypoxia-inducible factors (HIFs) build up and turn on many growth and blood-vessel genes like VEGF and PDGF. This makes the tumor grow, feed itself with new blood vessels, and sometimes spread to other parts of the body.
Clear cell carcinoma can stay silent for a long time. Many tumors are now found by chance when a person has an ultrasound or CT scan for another reason. Some tumors grow slowly and stay in the kidney. Others grow fast and may spread to the lungs, bones, liver, or brain. Early detection usually gives a much better chance of cure.
Other names
Doctors and books may use different names for the same disease. All the terms below usually mean clear cell carcinoma of the kidney:
Clear cell renal cell carcinoma (clear cell RCC)
Clear-cell renal-cell carcinoma (CCRCC)
Conventional renal cell carcinoma (older term)
Common type renal cell carcinoma (older descriptive term)
Kidney clear cell carcinoma
Clear cell adenocarcinoma of kidney (less common phrasing)
Older names like “hypernephroma” or “Grawitz tumor” were used in the past for kidney cancers, including clear cell type, but are now largely historical.
Types of clear cell carcinoma of kidney
Doctors can group clear cell carcinoma into a few simple types. These types are based on how the tumor starts, how far it has spread, and how the cells look under the microscope.
Localized clear cell carcinoma – The tumor is only in the kidney. It has not spread into nearby veins, lymph nodes, or other organs. Surgery can often cure this stage.
Locally advanced clear cell carcinoma – The tumor has grown into nearby tissues, the main kidney vein, or the large vein called the inferior vena cava. It may also reach nearby lymph nodes, but there is no spread to far-away organs. These tumors are harder to treat and need careful surgery and sometimes added medicines.
Metastatic clear cell carcinoma – Cancer cells have spread from the kidney to distant organs such as lungs, bones, liver, or brain. Treatment focuses on controlling the disease and helping the person live longer and better, using targeted therapy, immunotherapy, and sometimes surgery or radiation.
Hereditary clear cell carcinoma – Some people inherit a faulty gene, most often the VHL gene, as part of von Hippel–Lindau (VHL) syndrome. They can develop many kidney tumors at a younger age, and these tumors are often clear cell type.
Sporadic clear cell carcinoma – This is the most common type. It happens in people without an inherited syndrome. Gene changes, such as loss of the VHL gene and nearby genes like PBRM1, BAP1 and SETD2 on chromosome 3p, build up over time and help drive the cancer.
Low-grade clear cell carcinoma – Under the microscope, the tumor cells look more organized and calm. These tumors usually grow more slowly and may have a better outlook than high-grade ones.
High-grade or sarcomatoid clear cell carcinoma – The cells look very abnormal, may show sarcomatoid (spindle-cell) change, and often behave aggressively. These tumors are more likely to spread and have a poorer prognosis.
Causes and risk factors
For most people, there is no single clear cause. Instead, several risk factors raise the chance that normal kidney cells will collect DNA damage, lose tumor-suppressor genes like VHL, and turn into clear cell cancer.
Cigarette smoking – Smoking is one of the strongest and best-proven risk factors for kidney cancer, including clear cell type. Chemicals in tobacco smoke are filtered by the kidneys, damage kidney cells, and make DNA errors more likely. Smokers may have up to 50% higher risk than non-smokers.
Obesity (overweight) – Extra body fat changes hormone levels and increases insulin and growth factors, which push cells to divide more. Obesity is linked to around a quarter of kidney cancers and clearly raises the risk of renal cell carcinoma.
High blood pressure (hypertension) – Long-term high blood pressure damages the kidney’s small vessels and may promote cancer changes. The risk seems higher even after adjusting for medicines, so blood pressure itself is thought to play a role.
Older age – Kidney cancer is much more common in older adults. The average age at diagnosis is about 60–70 years. With age, cells collect more mutations, and the immune system becomes less able to remove abnormal cells.
Male sex – Men are about twice as likely as women to develop renal cell carcinoma. Hormones, lifestyle factors, and different exposure patterns may all contribute to this higher risk.
Family history of kidney cancer – Having a close relative (parent, brother, sister) with kidney cancer increases personal risk, even outside known hereditary syndromes. This suggests shared genes and shared environments play a part.
Von Hippel–Lindau (VHL) syndrome – People born with a harmful change in the VHL tumor-suppressor gene have a very high risk of multiple clear cell kidney tumors, often at younger ages. A second “hit” in the remaining copy of VHL in kidney cells can then trigger cancer.
Other hereditary kidney cancer syndromes – Conditions such as hereditary leiomyomatosis and renal cell cancer (HLRCC) and Birt–Hogg–Dubé (BHD) syndrome also raise renal cancer risk. BHD can lead to multiple kidney tumors, including clear cell RCC, chromophobe RCC, and hybrid tumors.
Chronic kidney disease (CKD) – Long-term kidney damage and scarring make the kidney tissue more unstable. CKD is linked with higher renal cancer risk, even after accounting for other factors like hypertension.
Long-term dialysis and acquired cystic kidney disease – People on dialysis for many years often develop many kidney cysts (acquired cystic kidney disease). These kidneys are more likely to form renal cell carcinoma, sometimes clear cell type.
Diabetes mellitus – Diabetes can injure kidney blood vessels and tubules. It often comes together with obesity and hypertension, which also raise risk. Some large studies have found higher kidney cancer risk in people with diabetes.
Unhealthy diet and low physical activity – Diets high in processed meat, red meat, and refined sugary foods, and low in fruits and vegetables, may increase risk through chronic inflammation and metabolic stress. Lack of exercise adds to weight gain and insulin resistance.
Occupational exposure to organic solvents (e.g., trichloroethylene) – Some studies link exposure to certain industrial chemicals, such as trichloroethylene and other chlorinated solvents, to a higher risk of renal cell carcinoma. Evidence is not perfect but is strong enough to raise concern.
Exposure to heavy metals (cadmium, lead) – Workers exposed to heavy metals, batteries, or some industrial dusts may have a higher kidney cancer risk. These substances can damage DNA in kidney cells.
Long-term use of some pain medicines (certain NSAIDs) – Years of heavy use of some non-steroidal anti-inflammatory drugs can injure kidney tissue. Some studies suggest this may slightly increase renal cell carcinoma risk, though the link is modest.
Previous radiation to the kidney area – Radiation used for other cancers in the abdomen or spine can damage kidney DNA. Many years later, this may contribute to new kidney tumors, though this is rare.
Metabolic syndrome (insulin resistance, high triglycerides) – A cluster of high blood sugar, abnormal lipids, and raised blood pressure increases general cancer risk, including kidney cancer, likely via chronic inflammation and hormone changes.
Acquired VHL gene mutation in kidney cells – In most sporadic clear cell cancers, both copies of the VHL gene are lost or inactivated by mutation or methylation during life. This molecular change is a key “driver cause” at the cell level.
Additional 3p gene losses (PBRM1, BAP1, SETD2, others) – After VHL loss, further changes in nearby tumor-suppressor genes like PBRM1, BAP1 and SETD2 help the tumor grow, invade, and become more aggressive.
General immune weakness or chronic inflammation – Long-term immune suppression (for example after some transplants) and chronic inflammatory states may reduce the body’s ability to clear abnormal cells, making cancer more likely to develop and progress.
Symptoms and signs
Many people with clear cell kidney cancer have no symptoms at first. Tumors are often found on scans done for other reasons. When symptoms do appear, they may be vague and develop slowly.
Blood in the urine (hematuria) – This is the most common symptom. Urine may look red, pink, or cola-colored, or blood may be seen only on a urine test. It is usually painless. Blood appears when the tumor breaks into tiny kidney tubes or the collecting system.
Flank or side pain – Dull or aching pain in the side, lower back, or flank can occur when the tumor stretches the kidney capsule, causes bleeding, or blocks urine flow. The pain is often on one side and may be constant or intermittent.
Palpable abdominal or flank mass – In some people, a doctor can feel a firm lump in the abdomen or flank during examination. This usually means the tumor is fairly large but can still be treatable.
Unexplained weight loss – Many people lose weight without trying. This can be due to loss of appetite, higher energy use by the tumor, or spread to other organs. Any significant, unexplained weight loss should be checked by a doctor.
Fever that comes and goes – Some patients have fevers not caused by infection. The tumor can release substances that reset the body’s temperature control, causing intermittent fever and sweating.
Tiredness and fatigue – Feeling very tired, weak, or lacking energy is common. This can be due to anemia (low red blood cells), chronic inflammation, poor sleep from pain, or other paraneoplastic effects.
Anemia (low red blood cells) – The tumor and chronic inflammation can interfere with red blood cell production, causing anemia. People may notice shortness of breath on exertion, pale skin, and fatigue. Blood tests usually show this early.
High blood pressure (secondary hypertension) – Renal tumors can increase production of renin and other hormones that raise blood pressure. Some people are first found to have cancer when severe or difficult-to-control hypertension is investigated.
Varicocele (mainly in men) – A new, large, or right-sided varicocele (swollen scrotal veins) that does not improve when lying down can be a sign of a kidney tumor pressing on or invading the testicular vein or inferior vena cava.
Leg swelling (edema) – Cancer pressing on large veins or causing heart and kidney strain can lead to swelling of both lower legs and ankles. This can also be related to blood clots from a hypercoagulable state in cancer.
Bone pain – If cancer has spread to bones, people may feel deep bone pain or have fractures after mild trauma. This is a serious sign and needs urgent medical review.
Persistent cough or shortness of breath – Spread to the lungs can cause cough, chest pain, or breathlessness. Sometimes small metastases are only seen on imaging before symptoms appear.
Night sweats and general malaise – Many people feel unwell, sweat at night, or feel “flu-like” without clear infection. These general symptoms often reflect systemic inflammation and cytokine release from the tumor.
High calcium levels (hypercalcemia) – Some tumors release substances like PTH-related peptide that raise blood calcium. This can cause thirst, frequent urination, confusion, belly pain, and constipation. It is a classic paraneoplastic effect in renal cell carcinoma.
Polycythemia (too many red blood cells) – Less often, the tumor makes excess erythropoietin, causing high red blood cell counts. People may have headaches, flushing, or blood clots. This is another paraneoplastic sign that should trigger a search for renal cell carcinoma.
Diagnostic tests
Doctors diagnose clear cell carcinoma of the kidney using a mix of history, physical exam, blood and urine tests, imaging, and sometimes a biopsy. In many cases, a kidney mass seen on CT or MRI with typical features is enough to diagnose renal cell carcinoma and plan treatment.
Physical examination tests
General physical examination and vital signs
The doctor starts by asking about symptoms, risk factors (such as smoking and blood pressure), and family history, then checks your pulse, blood pressure, temperature, and breathing. They look for signs like fever, weight loss, pallor from anemia, or leg swelling. These clues help the doctor suspect kidney cancer and decide which tests to order next.Abdominal inspection and palpation for a mass
The doctor gently presses on the abdomen and flanks to feel for a lump or enlarged kidney. A firm, non-tender mass that moves with breathing may suggest a kidney tumor. While this classic finding is now less common, it is still important, especially in larger tumors.Assessment for signs of paraneoplastic syndromes
During the exam, the doctor looks for clues of hormone-like effects from the tumor, such as high blood pressure, signs of high calcium (dehydration, confusion), or features of liver dysfunction without liver metastases (Stauffer syndrome). These patterns can point to renal cell carcinoma even before imaging.Examination of lymph nodes and other organs
The doctor feels lymph nodes in the neck, above the collarbone, and in the groin, and looks for enlarged liver or spleen. This helps check if the cancer might have spread beyond the kidney and guides staging and imaging choices.
Manual bedside tests
Bimanual palpation of the kidney
The doctor uses both hands, one in front and one behind the flank, to feel the kidney between them. This helps detect enlarged or irregular kidneys and can sometimes distinguish a kidney mass from liver or bowel masses.Ballottement of the kidney
In ballottement, the doctor uses a quick, gentle push from the back while the other hand feels in front. A large kidney may be felt “bouncing” between the hands. This simple bedside test helps confirm that a mass is attached to the kidney.Costovertebral angle (CVA) tenderness test
The doctor taps lightly over the area where the ribs meet the spine (the costovertebral angle). Tenderness there suggests irritation or stretching of kidney tissue or its capsule, which can occur with tumors, stones, or infection. This test is not specific for cancer, but it raises suspicion of a kidney problem.Performance status assessment (e.g., ECOG score)
The doctor asks how much daily activity you can do and whether you spend much of the day in bed or sitting. This “manual” functional test helps measure overall fitness, predict how well you may tolerate surgery or systemic therapy, and is used in all kidney cancer guidelines.
Lab and pathological tests
Urinalysis (urine test)
A simple urine test looks for blood, protein, sugar, infection, and sometimes cancer cells. Microscopic blood in the urine is very common in renal cell carcinoma, even when the urine looks normal to the eye. Urinalysis can also rule out infection as a cause of symptoms.Complete blood count (CBC)
A CBC measures red blood cells, white blood cells, and platelets. It can show anemia from chronic disease, high red cell counts from excess erythropoietin, or abnormal platelets. These findings help support the diagnosis and also check if you are fit for surgery or other treatments.Kidney function tests (serum creatinine, BUN, eGFR)
Blood tests for creatinine, blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR) show how well your kidneys are working. This is crucial before giving contrast dye for CT scans and before planning surgery, because removing a kidney will reduce kidney function further.Liver function tests and alkaline phosphatase
Blood tests for liver enzymes and alkaline phosphatase can reveal liver involvement or bone metastases. In some people with renal cell carcinoma, liver tests are abnormal without liver metastases (Stauffer syndrome), which is another paraneoplastic effect.Serum calcium and other electrolytes
High calcium levels are a common paraneoplastic problem in renal cell carcinoma. Measuring calcium, phosphate, and other electrolytes helps detect this, guide urgent treatment, and look for bone spread.Histopathology of kidney tumor (biopsy or nephrectomy specimen)
A pathologist examines tumor tissue under the microscope. The cells in clear cell carcinoma have pale, clear cytoplasm and distinct borders. The pathologist can confirm the subtype, grade the tumor, and sometimes test for markers like CAIX or key gene changes. Tissue often comes from the removed kidney, but needle biopsy is increasingly used when imaging is unclear or before ablative treatments.
Electrodiagnostic tests
Electrocardiogram (ECG)
An ECG records the heart’s electrical activity. It does not diagnose the kidney tumor itself but is important before major surgery or certain drugs. High calcium, anemia, or some treatments can affect the heart rhythm, so checking the ECG helps keep treatment safe.Echocardiogram (heart ultrasound)
An echocardiogram uses sound waves and electronic signals to show heart structure and pumping strength. Doctors may order it before big operations or intensive systemic therapy, especially if you have breathlessness, leg swelling, or a history of heart disease. Good heart function is important for handling treatment stress.
Imaging tests
Renal ultrasound
Ultrasound uses sound waves to create pictures of the kidneys. It is quick, painless, and has no radiation. Ultrasound can show if a mass is a simple fluid-filled cyst or a solid tumor and is often the first imaging test when kidney cancer is suspected or found accidentally.Contrast-enhanced CT scan of abdomen and pelvis
CT uses X-rays and a computer to make detailed cross-section images. With contrast dye, CT shows the size, shape, and enhancement pattern of the kidney mass and whether it has invaded veins, lymph nodes, or nearby organs. It is the main imaging test for diagnosing and staging renal cell carcinoma.MRI of the abdomen (and inferior vena cava)
MRI uses strong magnets and radio waves instead of X-rays. It is very helpful when CT contrast cannot be used or when doctors need to see if the tumor has grown into the main kidney vein or inferior vena cava. MRI can also help distinguish different tissue types and refine surgery plans.Chest imaging and bone scan for spread
A chest X-ray or chest CT is used to look for lung metastases, which are common sites of spread. If you have bone pain or high alkaline phosphatase, a bone scan or targeted MRI of bones may be done to check for bone metastases. These tests complete the staging picture and guide treatment decisions.
Non-pharmacological treatments
1. Surgical removal of the tumor (nephrectomy or partial nephrectomy)
Surgery is still the main non-drug treatment for clear cell kidney cancer that is limited to the kidney or nearby area. Partial nephrectomy removes only the tumor and a rim of normal kidney, and radical nephrectomy removes the whole kidney with nearby fat and sometimes lymph nodes. The purpose is to remove all visible cancer and give the best chance for cure in early stages. Mechanism is simple: physical removal of cancer tissue, which also reduces pain, bleeding, and pressure in later stages.
2. Ablation (cryoablation or radiofrequency ablation)
For small tumors or patients who cannot tolerate major surgery, doctors may use a needle to freeze (cryoablation) or burn (radiofrequency ablation) the tumor under imaging guidance. The purpose is to destroy cancer cells while keeping as much normal kidney as possible. The cold or heat damages cell membranes and proteins so the tumor cells die and are slowly absorbed by the body.
3. Active surveillance for very small, low-risk tumors
In older or frail people with small kidney tumors and many other health problems, immediate treatment may be more harmful than careful watching. Active surveillance means regular imaging scans and clinic visits instead of instant surgery. The purpose is to avoid over-treating slow-growing tumors. The mechanism is “time plus close monitoring”: if the tumor grows or changes, treatment is started promptly.
4. Palliative radiation therapy
Radiation is not the main curative treatment for clear cell kidney cancer, but it is very helpful to relieve pain from bone metastases, brain metastases, or bleeding lesions. The purpose is symptom control, not cure. High-energy beams damage the DNA of tumor cells in targeted areas, which shrinks tumors and reduces pressure on nerves and organs, improving quality of life.
5. Arterial embolization
In some patients, doctors block the blood supply to the kidney tumor by injecting tiny particles into the feeding artery. The purpose is to reduce bleeding risk, shrink the tumor before surgery, or relieve pain when surgery is not possible. Mechanism: cutting off blood flow starves the tumor of oxygen and nutrients, causing tumor cell death and volume reduction.
6. Structured physical activity program
Regular, gentle exercise like walking, cycling, or light strength training can improve fatigue, mood, and heart health in kidney-cancer patients. The purpose is to maintain muscle mass, support immune function, and lower risk of blood clots, high blood pressure, and weight gain. Mechanism: physical activity improves circulation, reduces inflammation, and supports hormone balance, which may also reduce long-term kidney-cancer risk.
7. Nutrition counselling by a renal-oncology dietitian
A trained dietitian can help design meals that protect remaining kidney function, keep weight stable, and reduce treatment-related side effects like nausea or constipation. The purpose is to make eating safe, enjoyable, and balanced. Mechanism: adjusting protein, salt, fluids, and fiber reduces strain on kidneys, stabilizes blood pressure, and supports healing during surgery and systemic therapy.
8. Smoking cessation support
Stopping smoking is vital because tobacco chemicals directly damage kidney cells and blood vessels and increase the risk of new cancers and heart disease. The purpose is to lower risk of further kidney damage and cancer progression. Mechanism: quitting reduces exposure to carcinogens, improves oxygen delivery, reduces inflammation, and enhances the body’s ability to respond to treatment.
9. Weight management and metabolic health programs
Obesity is a strong, modifiable risk factor for renal cell carcinoma. Healthy weight loss using diet, exercise, and sometimes bariatric counselling can reduce blood pressure, inflammation, and insulin resistance. The purpose is to lower future cancer risk and improve tolerance of treatment. Mechanism: reducing fat tissue changes hormone and growth-factor levels that drive tumor growth.
10. Blood pressure control through lifestyle
High blood pressure damages kidney tissue and is linked with both kidney cancer risk and poorer outcomes. Lifestyle steps like salt reduction, stress management, and weight control help. The purpose is to support kidney and heart health alongside medical therapy. Mechanism: lower blood pressure reduces mechanical stress on blood vessels and may reduce pro-tumor signals related to chronic vascular injury.
11. Palliative care and symptom-management services
Palliative care teams help manage pain, breathlessness, fatigue, nausea, sleep problems, and emotional stress at any stage, not only at the end of life. The purpose is to improve quality of life for patients and families. Mechanism: a team approach integrates medicine, nursing, psychology, and social work to relieve suffering and support decision-making.
12. Psychological counselling and psycho-oncology support
A diagnosis of clear cell kidney cancer can cause anxiety, depression, fear of recurrence, or post-traumatic stress. Talking therapy, cognitive-behavioral therapy, or group support can reduce distress. The mechanism is helping patients recognize unhelpful thought patterns, build coping skills, and stay engaged with treatment and daily life.
13. Social work, financial, and caregiver support
Cancer care is expensive and time-consuming. Social workers help with insurance, transport, work leave, and family roles. The purpose is to remove practical barriers to treatment adherence. Mechanism: by solving social and financial problems, patients can attend appointments, follow instructions, and reduce stress that harms mental and physical health.
14. Pain-management programs (non-drug techniques)
Non-drug methods like physiotherapy, heat or cold packs, guided relaxation, breathing exercises, and some complementary therapies (such as acupuncture or massage when safe) can reduce pain perception. Purpose is to limit reliance on strong painkillers and improve daily function. Mechanism: these methods change how the nervous system processes pain signals and improve muscle flexibility and blood flow.
15. Sleep hygiene and fatigue-management strategies
Cancer and treatment often disturb sleep and cause deep tiredness. Simple routines like regular bedtimes, limiting caffeine, relaxing before sleep, and light daytime activity can help. The purpose is to restore energy, mood, and concentration. Mechanism: better sleep supports hormone balance, immune function, and the body’s repair processes.
16. Infection-prevention measures
Hand hygiene, timely vaccines (like flu and pneumonia where appropriate), and avoiding crowded places during intense immunotherapy or targeted therapy can reduce infection risk. The purpose is to avoid delays in treatment and serious complications. Mechanism: lowering exposure to germs reduces the chance that a weakened immune system will be overwhelmed.
17. Advance care planning discussions
For advanced disease, early conversations about values, goals, and preferences (such as where the patient wants to be cared for, or which life-support treatments they would accept) are important. The purpose is to ensure care matches the patient’s wishes. Mechanism: documented plans guide the health-care team and family, especially in emergencies.
18. Participation in clinical trials
Clinical trials give access to new drugs, new combinations, or new ways of using existing treatments. The purpose is to possibly receive better therapy and to help improve care for future patients. Mechanism: close protocol-based follow-up and research-grade monitoring can also improve detection of side effects and disease changes.
19. Education and self-management training
Understanding the disease, treatment options, and side effects helps patients notice warning signs early and communicate better with their team. The purpose is shared decision-making. Mechanism: informed patients are more likely to adhere to medicines, attend visits, and ask for help promptly if something feels wrong.
20. Spiritual or meaning-centered care
Many people find strength in religious or personal beliefs. Chaplains or spiritual counsellors can help patients explore meaning, hope, and fears. The purpose is emotional and existential support. Mechanism: feeling connected, valued, and understood can reduce anxiety and improve overall well-being during cancer treatment.
Drug treatments
Safety reminder: The drug details below are summaries from FDA prescribing information and kidney-cancer guidelines. They are not dosing instructions for any individual. Only an oncologist can choose the right drug, dose, and schedule for a specific patient.
1. Sunitinib
Sunitinib is an oral targeted therapy that blocks several tyrosine kinases, including VEGF receptors, which tumors use to grow new blood vessels. It is approved for advanced renal cell carcinoma. Typical adult regimens use 50 mg once daily for 4 weeks followed by 2 weeks off, but schedules may vary in practice. Purpose is to slow tumor growth and shrink tumors by cutting off blood supply and blocking growth signals. Side effects can include fatigue, high blood pressure, hand–foot syndrome, diarrhea, and low blood counts.
2. Pazopanib
Pazopanib is another VEGF-targeted tyrosine kinase inhibitor taken by mouth. It is used for advanced RCC as a first-line or later treatment. Usual adult dosing is 800 mg once daily on an empty stomach, adjusted for side effects or interactions. The drug’s purpose is to inhibit tumor angiogenesis and growth pathways. Common side effects include liver-enzyme elevation, diarrhea, hair color changes, nausea, fatigue, and high blood pressure.
3. Cabozantinib
Cabozantinib is a multi-target TKI that blocks MET, VEGFR, and AXL, which are important in tumor growth and resistance. It is approved for previously treated RCC and in combination with nivolumab as first-line therapy for advanced RCC. Typical oral doses are 40–60 mg once daily, adjusted based on tolerance. Purpose is to slow disease progression and improve survival. Side effects include diarrhea, mouth sores, high blood pressure, fatigue, hand–foot syndrome, and risk of bleeding.
4. Axitinib
Axitinib is a highly selective VEGFR inhibitor used alone or together with pembrolizumab for advanced RCC. Standard doses are 5 mg twice daily, with adjustments up or down depending on side effects and blood pressure. Its purpose is to strongly block VEGF-driven angiogenesis. Common side effects are diarrhea, high blood pressure, fatigue, decreased appetite, and hand–foot syndrome.
5. Lenvatinib
Lenvatinib is a multi-kinase inhibitor that targets VEGFR, FGFR, and other pathways. It is approved in combination with pembrolizumab for first-line treatment of advanced RCC. Usual adult dosing in this combination is 20 mg once daily orally, adjusted for side effects. Purpose is to attack the tumor by both starving it of blood supply and amplifying the effect of immunotherapy. Side effects include high blood pressure, diarrhea, appetite loss, weight loss, and fatigue.
6. Everolimus
Everolimus is an oral mTOR inhibitor used as a later-line treatment for advanced RCC. It interferes with mTOR, a key protein in cell growth and metabolism. Typical adult dose is 10 mg once daily, with dose reductions if needed. Purpose is to slow cell division and reduce tumor size or growth rate. Side effects often include mouth ulcers, infections, high blood sugar or cholesterol, and fatigue.
7. Tivozanib
Tivozanib is a potent VEGFR TKI used for relapsed or refractory RCC in some regions. It is taken orally on a 3-weeks-on, 1-week-off schedule. The main goal is to provide long-lasting VEGF blockade with a tolerable side-effect profile. Common toxicities include high blood pressure, diarrhea, fatigue, and voice changes.
8. Pembrolizumab (KEYTRUDA)
Pembrolizumab is an immune checkpoint inhibitor that blocks PD-1 on T cells, helping the immune system recognize and attack cancer cells. It is approved with axitinib or lenvatinib for first-line treatment of advanced RCC and as adjuvant therapy after nephrectomy in high-risk patients. IV doses are usually weight-independent flat doses given every 3 or 6 weeks, based on the label. Side effects can include fatigue, rash, and “immune-related” problems like inflammation of lungs, liver, colon, or endocrine glands.
9. Nivolumab (OPDIVO)
Nivolumab is another PD-1 inhibitor used alone or in combination with ipilimumab or cabozantinib for advanced RCC. It is given by IV infusion at fixed doses every 2–4 weeks, depending on the regimen. Purpose is to re-activate exhausted T cells so they can destroy tumor cells. Side effects are similar to other PD-1 blockers, including fatigue, skin reactions, diarrhea, and immune-mediated organ inflammation.
10. Ipilimumab (YERVOY)
Ipilimumab targets CTLA-4, another immune checkpoint on T cells. In RCC it is combined with nivolumab, especially for people with intermediate or poor-risk advanced disease. It is usually given IV for four doses, together with nivolumab, then nivolumab continues alone. Purpose is a strong early “push” to the immune system to mount a broader anti-tumor response. Side effects can be serious immune-related reactions, including colitis, hepatitis, skin and hormone-gland problems.
11. Interleukin-2 (high-dose IL-2, where available)
Historically, high-dose IL-2 could produce long-term complete responses in a small number of selected patients with metastatic RCC, but with high toxicity. It is now used less often because newer immunotherapy combinations are safer and more effective. IL-2 is given IV in hospital under close monitoring. Side effects include low blood pressure, fluid leaks, kidney injury, and severe flu-like symptoms.
12. Interferon-alpha (older cytokine therapy)
Interferon-alpha is an older immune-stimulating drug once widely used in RCC. Today it is rarely used alone because targeted drugs and checkpoint inhibitors work better. It may still be used in some combinations or settings where newer drugs are not available. Side effects include flu-like symptoms, fatigue, mood changes, and blood-count problems.
13. Belzutifan (HIF-2α inhibitor)
Belzutifan is a newer oral drug that blocks HIF-2α, a key protein turned on when VHL is mutated in clear cell RCC. This directly targets a core driver of ccRCC biology. It is used in certain hereditary VHL-related tumors and, in some regions, for previously treated RCC. Common side effects include anemia, fatigue, and shortness of breath.
14. Sorafenib
Sorafenib is a multikinase inhibitor that also targets VEGFR and RAF kinases. It is an older TKI sometimes used when other options are not suitable. It is taken orally twice daily. Purpose is to slow tumor growth and angiogenesis. Side effects include hand–foot skin reaction, diarrhea, high blood pressure, and fatigue.
15. Axitinib + pembrolizumab combination
This specific combination uses axitinib for strong VEGF blockade and pembrolizumab for immune activation. It is a standard first-line regimen for many patients with advanced clear cell RCC. Mechanism is “double hit”: starving the tumor of blood and boosting immune attack at the same time. Side effects combine those of both drugs and need close monitoring of blood pressure, liver function, and immune-related events.
16. Nivolumab + ipilimumab combination
This regimen gives both PD-1 and CTLA-4 blockade. It is preferred for many patients with intermediate or poor-risk advanced ccRCC. The early combination phase is more intense, then nivolumab maintenance is given alone. The goal is deeper, longer-lasting immune control, sometimes leading to long remissions. Side effects can be stronger immune-related toxicities, so experienced teams and prompt management are essential.
17. Nivolumab + cabozantinib combination
Here, nivolumab boosts the immune system while cabozantinib targets multiple growth pathways important for RCC. It is approved as a first-line treatment in many settings. Purpose is high response rate and prolonged cancer control. The combination can cause diarrhea, high blood pressure, hand–foot syndrome, and immune-related issues, so close follow-up is needed.
18. Pembrolizumab + lenvatinib combination
This pairing offers powerful VEGF and FGFR blockade plus PD-1 inhibition. It is another first-line standard for advanced clear cell RCC. The goal is to shrink tumors quickly and extend survival. Side effects may include high blood pressure, diarrhea, fatigue, thyroid problems, and other immune-related conditions.
19. Adjuvant pembrolizumab after nephrectomy
In patients with high-risk clear cell kidney cancer after surgery, pembrolizumab may be given for about one year to reduce the chance of recurrence. Mechanism is to destroy microscopic cancer cells that remain in the body before they grow into visible metastases. Side effects are similar to other pembrolizumab uses and must be balanced against potential long-term benefit.
20. Supportive medicines (anti-emetics, bone-protective agents, etc.)
Although not aimed directly at the tumor, supportive drugs like anti-nausea medicines, growth-factor injections for low blood counts, or bone-strengthening drugs (bisphosphonates or denosumab) are important. They prevent or treat complications such as fractures, severe anemia, or infections. These medicines work by protecting normal tissues and allowing cancer therapy to continue safely.
Dietary molecular supplements
1. Omega-3 fatty acids (fish oil)
Omega-3 fats from fish oil or algae may help reduce inflammation and support heart health, which is important during cancer treatment. Typical supplement doses are in the range used for heart health, but must be adjusted with a doctor, especially if you take blood thinners. Mechanism: omega-3s are turned into anti-inflammatory molecules and may improve appetite and weight stability.
2. Vitamin D
Many kidney-cancer patients have low vitamin D levels, especially after surgery or with limited sun. Supplementation can support bone health and immune function when levels are low. The dose depends on blood tests and must be guided by a clinician to avoid toxicity. Mechanism: vitamin D helps regulate calcium and has roles in cell growth and immune regulation.
3. Protein supplements (when needed)
Some patients lose weight and muscle during treatment. Whey or plant-based protein powder, used under dietitian supervision, can help maintain strength without overloading the kidneys. The amount should follow individual protein targets per kilogram of body weight. Mechanism: adequate protein supports tissue repair, immune cells, and enzyme function.
4. Probiotics
Probiotic supplements may help restore a healthy gut microbiome when patients receive antibiotics or multiple drugs. A stable microbiome may improve digestion, reduce diarrhea, and possibly support immune responses. Doses and strains vary; they must be chosen carefully in immunocompromised patients. Mechanism: probiotics compete with harmful bacteria and strengthen the gut barrier.
5. Fiber supplements (psyllium or similar)
When diet is limited, fiber supplements can help relieve constipation from pain medicines or reduced activity. Doses are usually started low and increased with plenty of water. Mechanism: soluble fiber absorbs water and forms a soft gel that makes bowel movements easier and supports a healthy gut microbiome.
6. Oral rehydration and electrolyte solutions
During diarrhea, vomiting, or fever, balanced electrolyte drinks may prevent dehydration. Doses should be tailored to kidney function to avoid too much potassium or sodium. Mechanism: these solutions replace water and essential salts lost through the gut or sweat, supporting blood pressure and kidney perfusion.
7. Antioxidant-rich foods or mild supplements (vitamin C, E – with caution)
Small, diet-level doses of antioxidant vitamins from fruits and vegetables are usually preferred over high-dose pills. High doses of antioxidant supplements may interfere with some therapies, so they should only be used if your doctor agrees. Mechanism: antioxidants help neutralize excess free radicals and may reduce oxidative stress.
8. Calcium supplements (only if deficient)
After nephrectomy or with some drugs like everolimus, bone health can suffer. If dietary calcium is inadequate, carefully dosed supplements may be advised, often together with vitamin D. The dose is based on diet and blood tests. Mechanism: calcium is needed for bones, muscles, and nerves; correct levels prevent fractures and cramps.
9. Multivitamin at standard daily dose
A simple once-daily multivitamin can cover small gaps in intake when appetite is poor. High-dose or “megadose” products are not recommended. Mechanism: providing recommended daily amounts of vitamins and trace minerals supports general metabolism and immune function.
10. Plant-based omega-3 sources (flaxseed, chia)
Ground flaxseed or chia can add omega-3 fats and fiber to food. The amounts should fit into a kidney-safe diet. Mechanism: plant omega-3s and soluble fiber help control cholesterol, support bowel health, and may lower inflammation.
Immunity-boosting, regenerative, and stem-cell-related drugs
These are not simple “immune boosters.” They are powerful medical treatments used only under specialist supervision.
1. Immune checkpoint inhibitors (PD-1 blockers like pembrolizumab and nivolumab)
These drugs do not “boost” the immune system in a general way. Instead, they remove brakes (PD-1) from T cells, so the immune system can see and attack cancer cells better. This targeted immune activation can sometimes produce long-term responses in clear cell RCC, but it also risks serious autoimmune-type side effects that must be treated quickly with steroids or other medicines.
2. CTLA-4 inhibitor (ipilimumab)
Ipilimumab blocks CTLA-4, another checkpoint that normally dampens T-cell activation. In combination with nivolumab, it can create a strong, early burst of immune activity against tumor cells. This can lead to durable control in some patients, but immune-related toxicities can affect the gut, liver, skin, or endocrine glands, so close monitoring is essential.
3. Cytokine therapies (interleukin-2)
High-dose IL-2 stimulates T cells very strongly and was one of the first systemic treatments that produced complete, long-lasting remissions in a small group of metastatic RCC patients. Because it can cause severe low blood pressure, fluid shifts, and organ dysfunction, it is used only in highly selected, very fit patients at specialized centers.
4. Belzutifan (targeting HIF-2α in VHL-driven tumors)
Belzutifan works in a more “regenerative” sense by directly targeting a key abnormal pathway (HIF-2α) that drives blood-vessel growth and tumor survival in VHL-mutated clear cell RCC. By blocking HIF-2α, it may normalize some of the abnormal environment that tumors create. Anemia and hypoxia-related symptoms must be monitored during therapy.
5. Bone-targeted agents (bisphosphonates, denosumab)
When ccRCC spreads to bone, the cancer can cause bone breakdown and fractures. Bisphosphonates and denosumab act on bone-remodeling cells to slow bone loss and help prevent skeletal events. They do not kill kidney cancer cells directly but protect bone structure and reduce pain, supporting physical function and quality of life.
6. Experimental cellular and gene-based therapies (clinical trials)
Researchers are studying CAR-T cells, tumor-infiltrating lymphocytes, cancer vaccines, and other cell-based strategies in RCC. These therapies aim to create highly specific immune cells that recognize kidney-cancer antigens more strongly. At present they are available mostly in research settings, and their long-term role in clear cell RCC is still being defined.
Surgeries for clear cell kidney cancer
1. Partial nephrectomy (kidney-sparing surgery)
In partial nephrectomy, the surgeon removes only the tumor and a thin rim of normal kidney tissue. This is preferred for smaller tumors or when preserving kidney function is very important. It can be done through open, laparoscopic, or robotic techniques. The main reason for doing it is to cure the cancer while keeping as much healthy kidney as possible.
2. Radical nephrectomy
Radical nephrectomy removes the entire kidney, surrounding fat, and sometimes nearby lymph nodes and adrenal gland. It is used for larger or more complex tumors. The purpose is to remove all known disease from the primary site. After surgery, patients live with one kidney, so blood pressure, kidney function, and lifestyle need close follow-up.
3. Cytoreductive nephrectomy in metastatic disease
In some patients with metastatic clear cell RCC, removing the primary kidney tumor (even though metastases remain) can help symptoms and sometimes improve outcomes when combined with systemic therapy. The decision is complex and individualized. The mechanism is to reduce tumor burden, decrease bleeding or pain, and possibly improve immune responses and drug effectiveness.
4. Metastasectomy (removal of metastases)
If there are only a few metastatic spots, such as in lung, bone, or liver, surgeons may remove them surgically. The aim is to achieve complete visible tumor clearance or at least delay progression. This procedure can be combined with ablation or radiation. It works by physically removing resistant tumor deposits that are not controlled by drugs.
5. Palliative surgery for complications
Sometimes surgery is performed not to cure, but to fix problems like uncontrolled bleeding, urinary obstruction, or compression of nearby organs. Examples include stabilizing bones with metal rods or relieving blocked urine flow. The reason is to maintain comfort, prevent emergencies, and keep patients mobile and independent as long as possible.
Prevention and risk-reduction
Do not smoke or vape – Quitting tobacco is one of the most powerful ways to reduce kidney-cancer risk and protect your remaining kidney after treatment.
Maintain a healthy body weight – Balanced diet and regular movement reduce obesity-related hormonal changes that can promote RCC.
Control blood pressure – Lifestyle steps and medicines that keep blood pressure in range protect kidney blood vessels and may lower cancer risk.
Use pain medicines wisely – Long-term overuse of some painkillers can damage kidneys; always follow medical advice.
Limit exposure to harmful workplace chemicals – Follow safety rules if you work with solvents, heavy metals, or other kidney-toxic substances.
Stay physically active – Regular physical activity helps weight, blood pressure, and insulin control, all linked with lower RCC risk.
Manage diabetes and metabolic conditions – Good blood-sugar control reduces kidney damage and chronic inflammation.
Protect kidneys from other diseases – Early treatment of chronic kidney disease, infections, and stones may reduce future cancer risk.
Know your family history – People with hereditary syndromes (like VHL) should discuss screening and risk-reducing options with specialists.
Attend regular follow-up after treatment – Timely scans and lab tests catch recurrences early, when management is easier and more effective.
When to see a doctor
You should seek medical help immediately or urgently if you have any of these problems:
New or worsening blood in the urine, especially with clots.
Severe flank or back pain that does not improve or is associated with fever or vomiting.
Sudden shortness of breath, chest pain, or coughing blood.
Strong, unexplained headaches, confusion, or weakness in arms or legs.
These can be signs of complications like bleeding, blood clots, or spread of the disease and need urgent medical evaluation.
During and after treatment for clear cell kidney cancer, contact your oncology or urology team promptly if you notice:
Rapid weight loss, extreme fatigue, or loss of appetite.
New or worsening high blood pressure, swelling of legs, or shortness of breath.
Persistent diarrhea, severe skin rash, yellow eyes, or dark urine while on targeted or immune therapies.
Any fever above about 38°C, especially if you feel unwell or are on immunotherapy.
These may be side effects of drugs or signs that the cancer has changed, and early management can prevent serious harm.
What to eat and what to avoid
Eat plenty of colorful fruits and vegetables – Aim for a variety of colors each day to supply vitamins, minerals, and natural antioxidants; adjust potassium if your kidney function is low, under dietitian advice.
Choose lean and plant-based proteins – Fish, poultry, beans, and lentils are usually better than large amounts of red or processed meat for kidney and heart health.
Prefer whole grains over refined grains – Brown rice, oats, and whole-grain bread give steady energy and fiber, supporting gut and heart health.
Limit salt and salty processed foods – Too much salt raises blood pressure and strains the kidneys; avoid instant noodles, chips, fast food, and heavily salted snacks.
Stay well hydrated unless your doctor restricts fluids – Water is usually the best drink; sugary drinks and dark sodas are best limited because of sugar and phosphate content.
Avoid excessive alcohol – High alcohol intake harms the liver, raises blood pressure, and can interfere with medicines; ask your team about safe limits or if you should avoid alcohol entirely.
Be careful with herbal and “detox” products – Many herbal mixes are untested and some are directly toxic to kidneys or may interact with cancer drugs. Always check with your oncologist or pharmacist before starting any.
Limit very high-protein crash diets – Extreme high-protein eating plans can stress the kidneys, especially with reduced kidney mass after nephrectomy. Balanced protein according to your lab results is safer.
Watch phosphorus and potassium if kidney function falls – Some patients may need to limit very high-phosphate processed foods or very high-potassium fruits; this should be guided by blood tests and a renal dietitian, not guessed.
Focus on a balanced, enjoyable pattern – There is no single “kidney-cancer diet.” A flexible, culturally appropriate plan with plenty of whole foods, moderate protein, limited salt, and minimal ultra-processed foods is usually best.
Frequently asked questions (FAQs)
1. Is clear cell carcinoma of the kidney always aggressive?
No. Some clear cell tumors grow slowly, while others behave more aggressively. Stage (how far it has spread), grade (how abnormal the cells look), and risk scores help doctors predict behavior. Early-stage tumors removed completely by surgery can often be cured. Advanced disease can sometimes be controlled for many years with modern targeted and immune therapies.
2. Can lifestyle changes cure clear cell kidney cancer?
Lifestyle changes alone cannot cure clear cell kidney cancer. However, not smoking, staying active, eating well, and controlling blood pressure and weight can support treatment, reduce complications, and lower the risk of other serious illnesses. These steps work together with surgery and medicines, not instead of them.
3. Why are there so many different drug combinations?
Clear cell RCC has many growth pathways and can become resistant to single drugs. Combinations like PD-1 inhibitors with TKIs or CTLA-4 blockers attack the tumor in several ways at once. This can give higher response rates and longer survival but may also increase side effects, so choices are personalized.
4. How long will I need to take targeted pills or immunotherapy?
Duration depends on the drug, response, side effects, and guideline recommendations. Some regimens are given for a set time; others continue until disease progression or unacceptable toxicity. Your doctor will review scans and lab tests regularly to decide whether to continue, pause, or change treatment.
5. Can clear cell kidney cancer come back after surgery?
Yes, even after a “complete” nephrectomy, microscopic cancer cells can remain and cause recurrence months or years later. The risk depends on tumor size, grade, and other features. This is why regular follow-up scans and, in some high-risk cases, adjuvant pembrolizumab are recommended.
6. Is it safe to become pregnant after treatment?
Pregnancy after kidney-cancer treatment is a complex decision. Some systemic drugs can harm a developing baby and must be stopped for a safe “wash-out” period. Kidney function, blood pressure, and the risk of recurrence also matter. Patients should discuss plans with their oncology and obstetric teams well in advance.
7. Will I live a normal life with only one kidney?
Many people live full, active lives with a single kidney. However, they need regular checks of kidney function and blood pressure, and they should avoid things that damage kidneys, such as uncontrolled hypertension, heavy NSAID use, or extreme high-protein diets.
8. Are “natural” or herbal treatments safer than cancer drugs?
Not necessarily. Some herbs are harmless, but others can damage the liver or kidney or interfere with anticancer medicines. “Natural” does not mean “safe,” especially in high doses or mixtures. Always talk to your oncology team before using any herbal or alternative therapy.
9. Why do I feel so tired even when scans are stable?
Fatigue in kidney-cancer patients has many causes: anemia, medicines, emotional stress, sleep disruption, poor nutrition, and reduced activity. Stable scans do not mean the body is not working hard. Treating anemia, improving sleep, gentle exercise, and palliative-care support can help.
10. Is immunotherapy always better than TKIs?
Not always. For many patients, combinations of immunotherapy and TKIs give the best results, but some people cannot receive immunotherapy because of autoimmune disease or other reasons. In such cases, TKIs alone may still work well. Treatment decisions balance expected benefit, side effects, and patient preferences.
11. How often will I need scans?
Scan frequency depends on stage, treatment, and time since diagnosis. After surgery, scans may be done every 6–12 months initially; in advanced disease on systemic therapy, they are often done every 2–4 months. The schedule is individualized based on guidelines and your clinical course.
12. Can diet alone prevent kidney cancer?
No single food or diet can guarantee prevention. However, a healthy pattern with fruits, vegetables, whole grains, limited processed meat and salt, and normal body weight can reduce overall risk when combined with not smoking and good blood-pressure control.
13. Will exercise make the cancer spread faster?
Current evidence does not support the idea that moderate exercise speeds cancer spread. In fact, regular activity is associated with better physical function, mood, and possibly improved outcomes in many cancers. Programs should be tailored to your strength, symptoms, and doctor’s advice.
14. Are kidney-cancer treatments different in older patients?
Older people can benefit from the same modern therapies, but they may need dose adjustments and closer monitoring. Doctors look at “biologic age,” other diseases, and frailty, not just birth year, when choosing treatment. Supportive care is especially important in this group.
15. Where can I find reliable information and support?
Trusted information can be found from major cancer organizations, kidney foundations, and national cancer institutes. Patient groups and advocacy organizations also provide education and emotional support. Your oncology team can recommend resources that match your language, culture, and local health system.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 28, 2025.
