Onconephrology: Bridging Kidney Health and Cancer Treatment

Onconephrology is an overlap between kidney care and cancer care. It includes the diagnosis and management of kidney diseases in patients with cancer — such as those arising from malignancies, anti-cancer therapies or pre-existing kidney conditions.

Patients are referred to an onconephrologist when they develop kidney issues during or after cancer treatment, stem cell transplant or if they have chronic kidney disease prior to initiating therapy. Early involvement helps tailor the cancer treatments while minimizing adverse effects to the kidneys.

Understanding Nephrology and Cancer Care

Nephrology is the medical subspecialty dedicated to the study and treatment of kidney diseases. The kidneys play several vital roles in maintaining overall health, including:

• Filtering waste and toxins: Kidneys continuously filter blood, removing waste products, excess salts and toxins, which are then excreted from the body as urine.
• Fluid and electrolyte balance: They regulate the body's fluid levels and maintain a healthy balance of electrolytes like sodium, potassium and calcium.
• Blood pressure regulation: Kidneys produce hormones that help control blood pressure.
• Red blood cell production: They release a hormone called erythropoietin, which stimulates the bone marrow to produce red blood cells.
• Bone health: Kidneys are involved in activating Vitamin D, which is essential for bone health.

When kidney function is impaired, it can lead to a range of serious health problems, from acute kidney injury (a sudden loss of kidney function) to chronic kidney disease (a gradual, long-term decline in function), potentially requiring dialysis or a kidney transplant. A nephrologist is a doctor who specializes in diagnosing and treating these complex kidney conditions.

Impact of Cancer Treatment on Kidney Health

Anti-cancer therapies, including chemotherapy, immunotherapy, stem cell transplant and targeted agents, can cause acute kidney injury, proteinuria, glomerulonephritis, electrolyte imbalances or worsening of underlying chronic disease. These issues can compromise both kidney and cancer outcomes if not promptly addressed.

Certain agents — such as platin-based therapies, immune checkpoint inhibitors and anti-VEGF therapies — carry a higher risk for kidney damage. These treatments can lead to conditions like acute tubular injury, glomerulonephritis or thrombotic microangiopathy. They require close kidney monitoring and possibly dialysis.

Why Kidneys Are Vulnerable in Cancer Patients

The kidneys are particularly susceptible to damage in cancer patients due to several factors. This vulnerability stems from both the cancer itself and the various treatments used to combat it.

Direct Effects of Cancer on Kidneys

In some cases, the cancer itself can directly affect kidney function, leading to kidney injury or disease.

• Tumor-related obstruction: Tumors located in or near the urinary tract (kidneys, ureters, bladder) can grow large enough to block the flow of urine. This can cause urine to back up into the kidneys, leading to swelling and damage (hydronephrosis), which can impair kidney function.
• Paraneoplastic syndromes: These rare conditions occur when cancer-fighting immune cells or substances produced by the tumor mistakenly attack healthy cells in other parts of the body, including the kidneys. This can cause diseases that affect the kidney's filtering units.
• Electrolyte disorders: Certain cancers, especially those affecting bones or hormone-producing glands, can cause severe electrolyte imbalances. Hypercalcemia (high calcium levels in the blood) is a common complication of some cancers (e.g., multiple myeloma, breast cancer) and can directly damage the kidneys and impair their ability to concentrate urine. Other electrolyte abnormalities like high or low sodium, potassium or phosphorus can also be direct consequences of the tumor or its metabolic activity.
• Tumor lysis syndrome (TLS): This is a life-threatening complication that can occur when large numbers of cancer cells rapidly die and release their contents into the bloodstream. This typically happens after the initiation of chemotherapy for rapidly growing cancers like lymphomas or leukemias. The release of potassium, phosphate and nucleic acids can overwhelm the kidneys' filtering capacity, leading to severe electrolyte disorders, acute kidney injury and even kidney failure.
• Monoclonal gammopathies of renal significance (MGRS): These are a group of conditions where abnormal immune proteins (monoclonal gammopathies) produced by certain blood cancers, such as multiple myeloma or other plasma cell disorders, deposit in the kidneys. These protein deposits can directly damage the kidney's filtering units, leading to specific types of chronic kidney disease or acute kidney injury.

Kidney Issues from Cancer Treatment

While essential for fighting cancer, many cancer therapies can have kidney-damaging side effects.

• Nephrotoxicity of chemotherapy
  • Cisplatin: A widely used chemotherapy drug, cisplatin is known for its dose-dependent nephrotoxicity, causing damage to the kidney tubules and electrolyte abnormalities.
  • Methotrexate: High doses of this chemotherapy can crystallize in the kidney tubules, leading to obstruction and acute kidney injury if not managed carefully.
  • Ifosfamide: Can cause Fanconi syndrome, a disorder of the kidney tubules that impairs their ability to reabsorb nutrients and electrolytes, leading to their loss in urine.
  • Gemcitabine: Associated with thrombotic microangiopathy (TMA), a rare but severe complication that damages small blood vessels in the kidneys, leading to kidney injury and blood clotting issues.
  • Other agents: Many other chemotherapy drugs, including cyclophosphamide and platinum-based compounds, can also have varying degrees of kidney impact.
• Targeted therapies and kidney impact: Newer targeted therapies, while more precise, can also affect the kidneys.
• VEGF inhibitors (e.g., bevacizumab): These drugs block the growth of new blood vessels that tumors need to grow. However, they can also affect the blood vessels in the kidneys, leading to protein in the urine and high blood pressure, which can worsen kidney function.
• Tyrosine kinase inhibitors (TKIs): Used in various cancers (e.g., chronic myeloid leukemia, kidney cancer), some TKIs can cause kidney injury, including proteinuria and electrolyte imbalances.
• Immunotherapy and kidney injury: Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized cancer treatment by activating the immune system against cancer. However, this activation can sometimes lead to immune-related adverse events (irAEs), including acute kidney injury.
• Immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab): These drugs can cause various forms of kidney injury, most commonly acute interstitial nephritis, where the immune system attacks the kidney's tubules and surrounding tissue. The onset can be delayed, requiring careful monitoring.
• CAR T-cell therapy: This advanced therapy involves engineering a patient's own immune cells to fight cancer. While highly effective, it can lead to complications like cytokine release syndrome, which can indirectly cause acute kidney injury from inflammation.
• Radiation therapy: When radiation therapy is delivered to areas that include the kidneys, it can cause radiation nephritis, leading to chronic kidney disease or even kidney failure.
• Stem cell transplantation and kidney complications: Patients undergoing stem cell transplantation often face a high risk of kidney complications. These include:
• Kidney damage from conditioning regimens: High-dose chemotherapy and radiation used before transplant.
• Calcineurin inhibitor nephrotoxicity: Drugs like cyclosporine and tacrolimus, used to prevent graft-versus-host disease, are known to cause acute and chronic kidney injury.
• Thrombotic microangiopathy (TMA): Can occur as a complication of transplantation, often related to drugs or infections, leading to kidney damage.
• Post-transplant infections: Can also contribute to kidney injury.

Other Factors Affecting Kidney Health in Cancer Patients

Beyond direct effects of cancer and its treatments, several other factors can contribute to kidney problems in cancer patients.

• Pre-existing chronic kidney disease (CKD): Many cancer patients may already have some degree of kidney impairment due to age, diabetes, high blood pressure or other conditions. This pre-existing CKD makes them more vulnerable to the effects of cancer therapies and complicates treatment planning.
• Infections: Cancer patients, especially those undergoing chemotherapy, often have weakened immune systems, making them prone to severe infections (like sepsis) that can lead to acute kidney injury.
• Fluid and electrolyte imbalances: Vomiting, diarrhea, poor oral intake or fluid shifts due to illness can lead to dehydration and significant electrolyte disturbances, further stressing the kidneys.
• Surgery: Major cancer surgeries can sometimes lead to acute kidney injury due to blood loss, changes in blood pressure or the use of certain medications during and after the procedure.

The Role of Onconephrology in Patient Care

Onconephrologists collaborate with oncologists to evaluate baseline kidney function, adjust dosing and implement protective strategies. 

In patients with pre-existing kidney disease, oncologists and onconephrologists join efforts to tailor individualized treatment plans that balance effectiveness (from cancer standpoint) and safety (from kidney standpoint).

When to Consult an Onconephrologist

An onconephrologist plays a vital role in several scenarios.

• Before cancer treatment: To assess baseline kidney function, identify existing kidney disease and help oncologists select the safest and most effective cancer therapy, especially if potential kidney-damaging drugs are being considered. They can help adjust medication dosages to prevent kidney injury.
• During cancer treatment: To monitor kidney function, manage side effects like acute kidney injury, electrolyte disorders or high blood pressure and intervene promptly if kidney complications arise. They can also help distinguish between kidney issues caused by the cancer itself versus those caused by the therapy.
• After cancer treatment: To monitor for long-term kidney-related side effects, manage chronic kidney disease that may have developed and provide ongoing kidney care.
• In cases of kidney cancer: While oncologists manage the cancer itself, onconephrologists manage kidney function and any kidney-related complications, especially if a kidney is removed or impaired.
• For rare or complex kidney conditions: When a cancer patient develops an unusual or challenging kidney problem, such as a paraneoplastic glomerular disease or a specific drug-induced injury, the onconephrologist's specialized knowledge is invaluable.

Collaborative Care Model

One of the hallmarks of onconephrology is its emphasis on a multidisciplinary approach. Onconephrologists work closely with:

• Oncologists: To understand the cancer type, treatment plan and anticipated side effects.
• Radiation oncologists: To mitigate kidney exposure during radiation.
• Hematologists: Particularly for blood cancers and stem cell transplantation.
• Pharmacists: To manage drug interactions and adjust medication dosages for kidney function.
• Nurses: For monitoring and patient education.
• Dietitians: To provide nutritional guidance tailored to kidney health and cancer treatment needs.

This collaborative model ensures that patient care is holistic, considering both cancer eradication and the preservation of kidney function. Personalized treatment plans are developed, taking into account each patient's unique kidney health status, cancer type and overall health.

Services Offered by an Onconephrology Clinic

Specialized onconephrology clinics provide a comprehensive range of services tailored to the needs of cancer patients with kidney concerns.

• Baseline kidney function assessment: Thorough evaluation before starting cancer treatment to establish a baseline and identify risk factors.
• Risk stratification: Identifying patients at high risk for kidney complications based on their cancer type, planned therapy and existing medical conditions.
• Proactive prevention strategies: Implementing measures to prevent kidney injury, such as optimal hydration, careful selection of medications and pre-medication protocols.
• Early detection and diagnosis: Close monitoring for subtle changes in kidney function or urine tests, allowing for early diagnosis of complications.
• Management of acute kidney injury (AKI): Rapid assessment and management of sudden declines in kidney function, often involving fluid management, electrolyte correction and sometimes temporary dialysis.
• Management of chronic kidney disease (CKD): Ongoing management of long-term kidney impairment, including blood pressure control, diet modification and medication adjustments.
• Management of electrolyte disorders: Addressing imbalances in sodium, potassium, calcium and other electrolytes that are common in cancer patients.
• Blood pressure management: Controlling high blood pressure, which can be a side effect of some cancer therapies and can worsen kidney function.
• Consultation for specific kidney diseases: Expertise in diagnosing and managing paraneoplastic kidney diseases, thrombotic microangiopathy and other complex conditions.
• Education and support: Providing patients and their families with information about kidney health, potential complications and self-care strategies.

By providing these specialized services, onconephrology clinics strive to prevent kidney-related complications, mitigate their severity when they occur and ensure that cancer patients can continue receiving life-saving therapies with minimal impact on their kidney health.

Advancements and the Future of Onconephrology

Onconephrology is driven by the increasing complexity of cancer therapies and a deeper understanding of kidney-cancer interactions. Advancements in this subspecialty are focused on refining patient care and improving outcomes.

Research and Clinical Trials

Ongoing research is a cornerstone of onconephrology, with significant efforts directed towards:

• Understanding mechanisms of kidney injury: Researchers are working to better understand the precise ways in which new cancer therapies, such as immune checkpoint inhibitors and targeted agents, cause kidney damage. This involves studying cellular and molecular pathways to identify specific biomarkers that can predict kidney injury or indicate its onset early. For instance, studies are examining the role of specific immune cells and inflammatory mediators in immunotherapy-associated acute kidney injury.
• Development of renoprotective strategies: A major focus is on discovering and testing interventions that can protect the kidneys from damage caused by cancer treatments. This includes exploring novel drugs, adjusting dosing regimens of existing medications and implementing supportive care protocols. Clinical trials are vital in evaluating these strategies to ensure their safety and effectiveness.
• Risk prediction models: Developing sophisticated tools to identify which cancer patients are most likely to develop kidney complications based on their individual risk factors, genetic predispositions and the specific cancer therapy they receive. This allows for more targeted preventive measures.
• Long-term outcomes: Studying the long-term effects of cancer and its treatment on kidney health, including the progression of chronic kidney disease and the need for kidney replacement therapies years after cancer remission.

Emerging Therapies and Kidney Considerations

As new cancer therapies continue to emerge, onconephrology is constantly adapting. For instance:

• Novel immunotherapies: Beyond immune checkpoint inhibitors, newer forms of immunotherapy, such as bispecific antibodies and other adoptive cell therapies, are being developed. Onconephrologists are actively studying their potential kidney-related adverse events to inform guidelines for monitoring and management.
• Combination therapies: The use of multiple cancer drugs in combination is becoming more common. Understanding the cumulative and synergistic effects of these combinations on kidney function is crucial and an area of active research.
• Personalized medicine: Advancements in genetic profiling of tumors and patients are leading to increasingly personalized cancer treatments. Onconephrology aims to integrate this personalized approach by tailoring kidney protective strategies based on a patient's individual genetic makeup and risk factors for kidney damage.