The relationship between cancer and kidney health is complex and multifaceted. Cancer can affect the kidneys directly by originating in renal tissues (kidney cancer) or indirectly through metastatic spread. Metastatic spread refers to the process by which cancer cells break away from the original (primary) tumor and travel through the body to form new (secondary) tumors in other organs or tissues. This is a hallmark of cancer and a major cause of cancer-related morbidity and mortality.

Additionally, cancer treatments such as chemotherapy, radiation, and immunotherapy can have significant impacts on kidney function. This discussion explores the types of kidney cancer, the effects of cancer treatments on kidney health, the management of kidney health in cancer patients, and preventative measures.

Types of Kidney Cancer

Kidney cancer primarily includes renal cell carcinoma (RCC) and urothelial carcinoma (UC) of the renal pelvis.

• Renal Cell Carcinoma (RCC): RCC is the most common type of kidney cancer, accounting for about 90% of cases. It originates in the renal cortex, which is part of the kidney that filters blood and produces urine. Subtypes include clear cell RCC, papillary RCC, and chromophobe RCC, with clear cell RCC being the most prevalent.
• Urothelial Carcinoma (UC): UC of the renal pelvis accounts for 5-10% of kidney cancers. It arises from the urothelium, the lining of the renal pelvis that carries urine from the kidney to the bladder. UC is similar to bladder cancer in its behavior and treatment.

Cancer Treatments and Kidney Health

Cancer treatments, while often lifesaving, can lead to nephrotoxicity, adversely affecting kidney function.  Nephrotoxicity refers to kidney damage caused by exposure to toxic substances, which can include certain medications, environmental chemicals, or biological agents. The kidneys are particularly vulnerable to toxins due to their role in filtering blood and concentrating substances. The following is a discussion of nephrotoxicity as well as the main treatments with potential nephrotoxic effects:

• Chemotherapy: Agents such as cisplatin and methotrexate are known to cause acute kidney injury (AKI) and chronic kidney disease (CKD). Chemotherapeutic drugs can cause direct tubular injury, leading to nephritis and tubular necrosis.  Acute tubular necrosis is kidney injury caused by damage to the kidney tubule cells (kidney cells that reabsorb fluid and minerals from urine as it forms). Common causes are low blood flow to the kidneys (such as caused by low blood pressure), medications that damage the kidneys, and severe body wide infections. Furthermore, it is most commonly accepted that the most frequent causes of acute tubular necrosis are a stroke or a heart attack, conditions that reduce oxygen to the kidneys. Chemicals can also damage the tubules. These include X-ray contrast dye, anesthesia drugs, antibiotics and other toxic chemicals.
• Radiation Therapy: Radiation aimed at the abdomen or pelvis can inadvertently damage the kidneys. Radiation nephropathy can manifest as hypertension, proteinuria, and CKD.
• Immunotherapy: Drugs such as checkpoint inhibitors (e.g., nivolumab, pembrolizumab) can trigger immune-mediated kidney damage. This can result in various forms of nephritis, including interstitial nephritis. Interstitial nephritis is a kidney disorder in which the spaces between the kidney tubules become swollen (inflamed).
• Targeted Therapy: Tyrosine kinase inhibitors (e.g., sunitinib, sorafenib) used in RCC can cause hypertension and proteinuria, contributing to kidney damage.

Managing Kidney Health in Cancer Patients

Maintaining kidney health in cancer patients requires careful management and monitoring, including:

• Pre-Treatment Assessment: Baseline kidney function tests (serum creatinine, glomerular filtration rate) are essential before initiating cancer therapy. Identifying pre-existing kidney conditions helps tailor treatment plans to minimize renal risks.
• Hydration and Medication Adjustments: Adequate hydration is crucial to reduce nephrotoxicity, especially with chemotherapeutic agents. Dose adjustments or alternative drugs may be necessary for patients with impaired renal function.
• Monitoring During Treatment: Regular monitoring of kidney function tests during cancer treatment helps detect early signs of nephrotoxicity.
• Urinalysis to check for proteinuria and hematuria can provide early indications of renal impairment. Hematuria refers to bloody urine, and may be due to a problem in the kidneys or other parts of the urinary tract, such as cancer of the bladder or the kidney; and/or infection of the bladder, kidney, prostate, or urethra. Inflammation of the bladder, urethra, prostate, or kidney (glomerulonephritis)

Managing Complications:

Interventions such as diuretics for hypertension or corticosteroids for immune-mediated nephritis are critical. Renal replacement therapy (dialysis) may be required for severe AKI.

Preventative Measures

Preventing kidney damage in cancer patients involves a combination of lifestyle modifications and medical interventions:

Lifestyle Modifications: Hydration: Maintaining adequate fluid intake supports kidney function and helps flush out nephrotoxic agents.

• Diet: A balanced diet low in salt and rich in fruits and vegetables supports kidney health and overall well-being.
• Avoiding Nephrotoxins: Limiting the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other nephrotoxic medications is essential.

Medical Interventions:

• Prophylactic Measures: Use of agents like amifostine to protect against cisplatin-induced nephrotoxicity. * AMIFOSTINE (am i FOS teen) is a protective medicine. It is used to prevent or lessen the kidney damage that can be caused by cisplatin chemotherapy. It is also used to prevent some side effects caused by radiation therapy to the head or neck.
• Nephrotoxicity describes the process that occurs when kidneys are damaged by a drug, chemical or toxin, resulting in possible chronic kidney disease. Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants.

Prophylactic, in medical terms, refers to any measure taken to prevent disease or a specific health problem rather than treating it after it occurs. Prophylactic measures can include medications, vaccines, lifestyle changes, surgical procedures, or any interventions aimed at preventing the onset or worsening of a condition.

Types of Prophylactic Measures

Medications:

• Antibiotics: Given to prevent infections, especially in situations where there’s a high risk of infection, such as before certain surgeries.
• Antiviral drugs: Used to prevent viral infections, like antiretroviral drugs for preventing HIV transmission.

Hydration and Kidney Protection in Chemotherapy: Patients undergoing chemotherapy are advised to maintain adequate hydration to help flush out nephrotoxic agents and reduce the risk of kidney damage.

Vaccination and Infection Control: Vaccinations can prevent infections that might lead to complications in cancer patients with compromised immune systems, indirectly protecting kidney function.

Preventive Medications: For example, using bisphosphonates or denosumab in cancer patients with bone metastases to prevent skeletal-related events, thus reducing the risk of kidney damage from hypercalcemia. Bisphosphonates are a group of drugs that work by slowing bone loss. They reduce the risk of hip and spine fractures. Bone renewal is a slow process, but in many people an increase in bone density can be measured over five years of treatment.

Regular Monitoring and Early Detection: Regular kidney function tests and urinalysis in cancer patients can help detect early signs of nephrotoxicity, allowing for timely interventions to prevent further damage.

Importance of Prophylactic Measures

• Improving quality of life: Preventing diseases or complications can significantly enhance the quality of life.
• Cost-effective: preventing a disease is often more cost-effective than treating it after it occurs.
• Reducing morbidity and mortality: Prophylactic measures can reduce the incidence of serious health conditions, leading to lower morbidity and mortality rates.
• Enabling effective treatment: In cancer patients, preventing kidney damage ensures that the patient can continue with their necessary cancer treatments without interruption.

In conclusion, prophylactic measures are essential in both general healthcare and in the specific context of cancer and kidney health, offering a proactive approach to health maintenance and disease prevention.

Chemopreventive agents: Medications like tamoxifen for high-risk breast cancer patients to reduce the risk of developing breast cancer. Furthermore, Chemopreventive agents include the use of certain drugs or other substances to help lower a person’s risk of developing cancer or keep it from coming back. For example, tamoxifen and raloxifene are drugs that may be used to prevent certain types of breast cancer in women who are at high risk of developing the disease.

Early Detection: Regular screening for kidney function in high-risk patients helps in early intervention.

Patient Education: Informing patients about the signs and symptoms of kidney injury ensures prompt reporting and management.

Kidney Cancer Risk Factors and Prevention

Understanding the risk factors for kidney cancer can aid in prevention strategies:

• Smoking: Increases the risk of RCC and UC.
• Obesity: Linked to higher risk due to hormonal and metabolic changes.
• Hypertension: Both a risk factor and a consequence of kidney disease.
• Family History: Genetic predisposition plays a role in RCC.

• Prevention: Smoking Cessation: Reduces the risk of developing kidney cancer and other malignancies;
• Weight Management: Maintaining a healthy weight through diet and exercise.
• Blood Pressure Control: Effective management of hypertension reduces kidney cancer risk.

Cancer and kidney health are intricately linked, with cancer having the potential to affect the kidneys directly through renal malignancies or indirectly through treatment-related nephrotoxicity. Managing kidney health in cancer patients requires a multifaceted approach, including pre-treatment assessments, vigilant monitoring, and appropriate interventions. Preventative measures and lifestyle modifications play a critical role in minimizing risks and preserving kidney function. Awareness and proactive management can significantly improve outcomes for cancer patients, ensuring better quality of life and enhanced treatment efficacy.