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Kidney Cancer

Disease Details

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Description: Kidney cancer, or renal cell carcinoma, is a type of cancer that starts in the cells of the kidneys, which are responsible for filtering blood and producing urine.
Type: Kidney cancer, also known as renal cancer, can be classified into several types, the most common of which is renal cell carcinoma (RCC). In terms of genetic transmission, most cases of kidney cancer are sporadic, meaning they occur by chance and are not inherited. However, there are hereditary forms of kidney cancer, such as von Hippel-Lindau (VHL) syndrome and hereditary papillary renal carcinoma (HPRC), which follow an autosomal dominant pattern of inheritance.
Signs And Symptoms: Early on, kidney masses do not typically cause any symptoms and are undetectable on physical examination. As kidney cancer becomes more advanced it classically results in blood in the urine, flank or back pain, and a mass. Other symptoms that are consistent with advanced disease include weight loss, fever, night sweats, palpable swollen lymph nodes in the neck, non-reducing varicocele, bone pain, continuous cough, and bilateral lower leg swelling.The classic triad of visible blood in the urine (hematuria), flank pain and palpable abdominal mass occurs in less than 15% of the cases. RCC may present with signs and symptoms caused by the substances the cancer cell produce (i.e. paraneoplastic syndromes).Paraneoplastic syndromes caused by kidney cancer can be broadly classified as endocrine and non-endocrine. Endocrine dysfunctions include increase in blood calcium levels (hypercalcemia), high blood pressure (hypertension), increased red bloods (polycythemia), liver dysfunction, milky nipple discharge unrelated normal breast-feeding (galactorrhea), and Cushing's syndrome. Non-endocrine dysfunctions include deposition of protein in tissue (amyloidosis), decrease in hemoglobin or red blood cells (anemia), disorders of nerves, muscles (neuromyopathies), blood vessels (vasculopathy) and blood clotting mechanisms (coagulopathy).
Prognosis: The prognosis for kidney cancer (renal cancer) depends on several factors, including the stage at diagnosis, the histological type of cancer, the patient's overall health, and response to treatment. Early-stage kidney cancer (localized to the kidney) has a better prognosis, with a relatively high 5-year survival rate. For localized renal cell carcinoma (RCC), the 5-year survival rate can exceed 90%. If the cancer has spread beyond the kidney (metastatic stage), the prognosis is poorer, with a significantly reduced 5-year survival rate, often below 15%. Treatment advancements have improved outcomes, but individual prognosis can vary widely.
Onset: Kidney cancer, also known as renal cell carcinoma, typically does not show early symptoms. When symptoms do appear, they may include blood in the urine, persistent back pain, weight loss, fatigue, and intermittent fever. There is no direct involvement of nanoparticles (nan) in the common presentations of this disease, though research into nanotechnology for diagnosis and treatment is ongoing.
Prevalence: Kidney cancer, also known as renal cancer, is relatively uncommon but still a notable health concern. In the United States, it represents about 3-5% of all adult cancers. Annually, there are approximately 73,000 new cases and about 15,000 deaths related to kidney cancer. Globally, kidney cancer accounts for roughly 2-3% of all cancers, with variations in prevalence depending on geographic and demographic factors.
Epidemiology: Around 208,500 new cases of kidney cancer are diagnosed in the world each year, accounting for just under 2% of all cancers. The highest rates are recorded in North America and the lowest rates in Asia and Africa.Lifestyle risk factors
Certain lifestyle factors have been associated with the development of renal cancer, although not all of them can be considered definitive causes. These include smoking, chemical carcinogens, radiation, viruses, diet and obesity, hypertension, diuretics, and alcohol consumption. Only a small percentage of kidney cancer cases have been linked to genetic factors. With obesity listed as one of the risk factors, daily physical activity and engaging in a healthy diet is proven to lower the rates of developing kidney cancer in the future.Age
The incidence rate of renal cancer increases with the age of an individual, with 75 being the approximate age of the peak incidence rate, as of 2018. However, nearly one half of all cases are diagnosed before the age of 65. In both male and female children, renal tumors represent 2% to 6% of kidney cancer, with Wilms' tumor being the most common.
Sex
The incidence of kidney cancer is two times greater in men than in women, and this is thought to be due to biological differences. Mortality rates typically decrease more rapidly in women compared to men.International variations
Incidence rates of kidney cancer can vary throughout the world. As of 2018, Czech Republic and Lithuania have the highest incidence rate of kidney cancer worldwide, with an age-standardized rate of 21.9/100,000 in males (Czech Republic) and 18.7/100,000 in males (Lithuania.) China, Thailand, and African countries (low-risk countries) have an incidence rate that is less than 2/100,000.Since the early 2000s, Austria and Poland have been the only countries to report a decrease in kidney cancer rates.Diagnosis access bias plays a large role in the epidemiology of kidney cancer. Differences in kidney cancer diagnosis across regions are likely due to differences in healthcare access, rather than a population's biological factors. Discrepancies in kidney cancer diagnosis has most likely led to the underrepresentation of mortality and incidence in low income countries.
Race
Race and ethnicity may be a factor in the distribution of kidney cancer around the United States. There are higher incidence rates in Black men and Hispanics, an average rate for American Indians, and low rates in Asians in the United States. Black people with kidney cancer have lower mortality rates than Caucasians in the United States.Screening
Accessibility for cancer screening is not very common due to high expenses. Improving cancer registries can improve care to those who have kidney cancer as well as decreasing the incidence and death rates. Safe and dependable treatment is key with the screening and treatment, which is not always the case in many developing nations.
Intractability: Kidney cancer, depending on its stage and type, can vary in terms of treatment difficulty and outcomes. Early-stage kidney cancers are often treatable with surgical interventions, such as nephrectomy, and may have a good prognosis. Advanced stages of kidney cancer, particularly those that have metastasized, can be more challenging to treat. Targeted therapies and immunotherapies have improved outcomes but do not guarantee a cure. Thus, while not universally intractable, kidney cancer can present significant treatment challenges, especially in advanced stages.
Disease Severity: Kidney cancer severity can vary widely. It depends on various factors such as the type of kidney cancer (e.g., renal cell carcinoma, transitional cell carcinoma), the stage at which it is diagnosed, and the overall health of the patient. Early-stage kidney cancer confined to the kidney may have a better prognosis and is often treatable with surgery. Advanced stages, where the cancer has spread to other parts of the body, generally have a poorer prognosis and may require more comprehensive treatments like targeted therapy, immunotherapy, or chemotherapy. The presence of certain genetic mutations and the patient's response to treatment also play significant roles in determining the severity and overall prognosis of the disease. Regular monitoring and follow-ups are essential for managing kidney cancer effectively.
Healthcare Professionals: Disease Ontology ID - DOID:263
Pathophysiology: Pathophysiology of kidney cancer involves the transformation of normal kidney cells into malignant cells, leading to uncontrolled growth and tumor formation. Typically, renal cell carcinoma (RCC) is the most common type of kidney cancer, originating in the renal cortex. Genetic mutations, such as in the VHL gene, loss of function in tumor suppressor genes, and changes in other oncogenes, play critical roles. These genetic changes disrupt normal cellular mechanisms, promoting angiogenesis (formation of new blood vessels), increased cell survival, and proliferation. This unregulated growth results in the formation of cancerous tumors within the kidney.
Carrier Status: Kidney cancer does not typically involve a "carrier status" as seen with some genetic diseases. Most cases of kidney cancer are sporadic, meaning they occur by chance and are not inherited. However, there are hereditary conditions, such as von Hippel-Lindau disease, hereditary papillary renal carcinoma, and Birt-Hogg-Dubé syndrome, that can increase the risk of developing kidney cancer. People with these hereditary conditions can be considered at higher risk but are not "carriers" in the traditional sense used for single-gene autosomal recessive disorders.
Mechanism: Kidney cancer, also known as renal cell carcinoma (RCC), primarily arises from the epithelial cells of the renal tubules. The mechanisms and molecular pathways involved in kidney cancer are complex and multifaceted.

### Mechanism:
The pathogenesis of kidney cancer typically involves both genetic predispositions and environmental factors. Common risk factors include smoking, obesity, hypertension, and chronic kidney disease. The disease progresses as normal renal cells transform into malignant ones, driven by a combination of genetic mutations and changes in cellular regulatory mechanisms.

### Molecular Mechanisms:
1. **Von Hippel-Lindau (VHL) Gene Inactivation**: The VHL gene is frequently mutated or silenced in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. The VHL protein regulates hypoxia-inducible factors (HIFs). When VHL is inactivated, HIFs accumulate, leading to increased transcription of genes that promote angiogenesis (e.g., VEGF) and cell proliferation.

2. **mTOR Pathway Activation**: The mammalian target of rapamycin (mTOR) signaling pathway is often upregulated in kidney cancer. This pathway plays a key role in cell growth, proliferation, and survival. Mutations in genes encoding components of this pathway, such as PTEN and PI3K, can lead to its dysregulation.

3. **MET and HGF**: The MET proto-oncogene encodes a receptor tyrosine kinase that is activated by hepatocyte growth factor (HGF). Abnormal activation of the MET/HGF pathway can contribute to the progression and spread (metastasis) of kidney cancer.

4. **Epigenetic Changes**: In addition to genetic mutations, epigenetic alterations such as DNA methylation, histone modification, and non-coding RNA expression (e.g., microRNAs) play a significant role in RCC. These changes can affect gene expression without altering the DNA sequence.

5. **PBRM1, BAP1, and SETD2 Mutations**: These genes are frequently mutated in RCC and are involved in chromatin remodeling and gene transcription regulation. Their inactivation can contribute to oncogenesis by disrupting normal cellular processes.

Understanding these mechanisms is critical for developing targeted therapies and improving treatment outcomes for kidney cancer patients.
Treatment: Treatment for kidney cancer depends on the type and stage of the disease. Surgery is the most common treatment as kidney cancer does not often respond to chemotherapy and radiotherapy. Surgical complexity can be estimated by the RENAL Nephrometry Scoring System. If the cancer has not spread it will usually be removed by surgery. In some cases this involves removing the whole kidney however most tumors are amenable to partial removal to eradicate the tumor and preserve the remaining normal portion of the kidney. Surgery is not always possible – for example, the patient may have other medical conditions that prevent it, or the cancer may have spread around the body and doctors may not be able to remove it. If the cancer cannot be treated with surgery other techniques such as freezing the tumour or treating it with high temperatures may be used. However, these are not yet used as standard treatments for kidney cancer. Recently, evidence stemming from the KEYNOTE-564 study has shed light on the potential use of systemic therapy in the adjuvant setting, with promising results. Patients exhibiting specific clear cell RCC tumor characteristics and having undergone treatment with Pembrolizumab for 17 cycles (around 1 year) had significant improvement in disease-free survival. However, the study has yet to yield conclusive findings in relation to overall survival. Other treatment options include biological therapies such as everolimus, torisel, nexavar, sutent, and axitinib, the use of immunotherapy including interferon and interleukin-2. Immunotherapy is successful in 10 to 15% of people. Sunitinib is the current standard of care in the adjuvant setting along with pazopanib; these treatments are often followed by everolimus, axitinib, and sorafenib. Immune checkpoint inhibitors are also in trials for kidney cancer, and some have gained approval for medical use.In the second line setting, nivolumab demonstrated an overall survival advantage in advanced clear renal cell carcinoma over everolimus in 2015 and was approved by the FDA. Cabozantinib also demonstrated an overall survival benefit over everolimus and was approved by the FDA as a second-line treatment in 2016. Lenvatinib in combination with everolimus was approved in 2016 for patients who have had exactly one prior line of angiogenic therapy.In Wilms' tumor, chemotherapy, radiotherapy and surgery are the accepted treatments, depending on the stage of the disease when it is diagnosed.
Compassionate Use Treatment: Compassionate use treatment for kidney cancer allows patients with advanced kidney cancer access to experimental therapies that are not yet approved by regulatory agencies. These treatments are typically considered when no alternative therapy exists and the patient is not eligible for clinical trials.

Off-label treatments might include the use of drugs approved for other cancers or conditions that have shown potential benefits in kidney cancer. Examples include certain immunotherapy agents and newer targeted therapies that may not have specific approval for kidney cancer but have demonstrated efficacy in related malignancies.

Experimental treatments often evaluated in clinical trials for kidney cancer can involve a range of innovative approaches:

1. Combination Therapies: Combining checkpoint inhibitors with other agents like anti-angiogenic drugs or additional immunotherapies.
2. Novel Targeted Therapies: Agents targeting specific mutations or pathways relevant to kidney cancer.
3. Personalized Medicine: Tailoring treatment based on the genetic profile of the tumor.

Patients considering compassionate use, off-label, or experimental treatments should consult with their healthcare providers to weigh the potential risks and benefits.
Lifestyle Recommendations: For kidney cancer, the following lifestyle recommendations can be beneficial:

1. **Diet and Nutrition:** Emphasize a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Avoid excessive red meat and processed foods.

2. **Physical Activity:** Engage in regular physical activity such as walking, cycling, or swimming to maintain a healthy weight and improve overall health.

3. **Healthy Weight:** Maintain a healthy weight, as obesity is a risk factor for kidney cancer.

4. **Avoid Tobacco:** Do not smoke or use tobacco products; smoking increases the risk of kidney cancer.

5. **Limit Alcohol:** Limit alcohol consumption as excessive drinking can contribute to various health issues.

6. **Hydration:** Drink plenty of water to support kidney function and general health.

7. **Regular Check-ups:** Have regular medical check-ups, especially if you have risk factors for kidney cancer such as a family history of the disease or genetic predisposition.

8. **Manage Medical Conditions:** Properly manage underlying medical conditions such as hypertension and diabetes which can affect kidney health.

9. **Avoid Exposure to Harmful Chemicals:** Limit exposure to harmful chemicals and substances that can increase cancer risk, such as certain herbicides and solvents.

Consult with healthcare providers for personalized advice based on individual health status and risk factors.
Medication: Medications for kidney cancer can include targeted therapies, immunotherapy, and sometimes chemotherapy. Commonly used targeted therapies are tyrosine kinase inhibitors like sunitinib and pazopanib. Immunotherapy options include checkpoint inhibitors such as nivolumab and pembrolizumab. The choice of medication depends on the specific characteristics of the cancer and the patient's overall health.
Repurposable Drugs: Repurposable drugs for kidney cancer include:

1. **Metformin**: Traditionally used for type 2 diabetes, it has shown potential anticancer effects through AMPK activation and mTOR inhibition.
2. **Aspirin**: An anti-inflammatory drug that may reduce cancer risk and inhibit tumor growth by affecting cyclooxygenase (COX) enzymes.
3. **Statins**: Cholesterol-lowering medications that may impede cancer cell proliferation and induce apoptosis.
4. **Thalidomide**: Known for its immunomodulatory properties, it has been investigated for anti-angiogenic effects in kidney cancer.

These drugs are being studied for their potential to be repurposed in the treatment of kidney cancer due to their various mechanisms of action that may affect cancer cell growth and survival.
Metabolites: In kidney cancer, several metabolites can be relevant for diagnostic and prognostic purposes. Altered metabolism is a hallmark of cancer cells, including those in the kidneys. Commonly studied metabolites in kidney cancer include:

1. Lactate: Often elevated due to increased glycolysis (Warburg effect).
2. Glutamine: Utilized in large amounts by cancer cells for energy and growth.
3. TCA cycle intermediates: Such as citrate, succinate, and fumarate which may show altered levels.
4. Amino acids: Some, like serine and glycine, may be upregulated to support rapid cell division and growth.
5. Lipid metabolites: Variations in lipid metabolism are often observed, including changes in fatty acid synthesis and beta-oxidation.

Specific metabolomic profiles can vary depending on the type and stage of kidney cancer, and advanced techniques like mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy are typically used to analyze these metabolites in detail.
Nutraceuticals: Currently, there is no substantial scientific evidence to support the effectiveness of nutraceuticals in treating or preventing kidney cancer. Nutraceuticals, which include vitamins, minerals, herbs, and other dietary supplements, may offer various health benefits, but their role in cancer therapy remains unclear. Patients should consult with healthcare providers before using any nutraceuticals, as they might interact with conventional cancer treatments or have unintended side effects.
Peptides: Peptides in the context of kidney cancer may refer to specific protein fragments that can be used for therapeutic purposes, such as targeted drug delivery or immunotherapy. These peptides can be designed to target cancer cells specifically, potentially improving treatment efficacy and reducing side effects.

Nanotechnology (nan) in kidney cancer involves the use of nanoparticles to improve diagnosis, imaging, and treatment. Nanoparticles can be engineered to deliver drugs directly to cancer cells, enhance the visibility of tumors through imaging techniques, and even assist in the destruction of cancer cells through methods like photothermal therapy. These advanced approaches aim to provide more precise and effective treatments for kidney cancer.