Kidney failure, defined as the loss of the kidneys’ ability to filter waste and regulate fluids, is a serious clinical concern that can develop at any stage of a cancer diagnosis. Acute kidney injury (AKI) is particularly common, sometimes occurring in up to half of all patients during the course of their disease. Understanding the mechanisms behind this organ damage—whether caused by the tumor itself or by medical treatments—is fundamental to preserving kidney function.
Direct Mechanisms of Cancer-Related Kidney Damage
Cancer can directly impair kidney function through physical obstruction or through the release of potent metabolic byproducts into the bloodstream. Obstructive nephropathy occurs when a growing tumor or enlarged lymph nodes physically block the flow of urine from the kidney down the ureters and into the bladder. This back-up of pressure causes the renal pelvis to swell, a condition called hydronephrosis, which mechanically damages the delicate filtering units inside the kidney. Cancers in the pelvis, such as those of the prostate, cervix, bladder, or colon, are common causes of this post-renal blockage.
Many cancers, particularly hematologic malignancies like multiple myeloma or lymphomas, can cause damage through systemic metabolic disturbances. In multiple myeloma, the overproduction of abnormal light chain proteins can saturate the kidney’s filtration capacity. This leads to the formation of casts that directly clog the renal tubules. This is known as myeloma cast nephropathy, which is a frequent cause of AKI in these patients.
Other tumors can cause paraneoplastic syndromes, which are effects distant from the primary tumor site, such as the excessive secretion of Parathyroid Hormone-related Peptide (PTHrP). This PTHrP mimics natural parathyroid hormone, causing calcium to be released from the bones and increasing its reabsorption in the kidneys, resulting in hypercalcemia. High levels of calcium damage the kidneys by inducing vasoconstriction, which reduces blood flow and filtration rate. Excessive calcium also interferes with the kidney’s ability to concentrate urine, causing profound volume depletion that contributes to AKI.
A sudden metabolic threat is Tumor Lysis Syndrome (TLS), which occurs when a rapidly growing tumor spontaneously releases its entire cellular contents into the circulation. The massive influx of intracellular components includes potassium, phosphate, and nucleic acids, which are metabolized into uric acid. The high concentration of uric acid and the subsequent precipitation of calcium phosphate crystals mechanically obstruct the renal tubules, causing severe AKI. This medical emergency is most often associated with high-grade lymphomas and acute leukemias.
Kidney Toxicity from Cancer Treatments
Anti-cancer therapies carry a risk of damaging healthy kidney tissue, a side effect known as nephrotoxicity. Cisplatin, a platinum-based chemotherapy drug, is notorious for causing direct damage to the cells lining the proximal tubules. This damage often results in dose-dependent Acute Tubular Necrosis (ATN) and can lead to a long-term decline in renal function. Similarly, high-dose methotrexate can precipitate as crystals in the renal tubules, causing obstruction and kidney injury if not flushed out with aggressive intravenous hydration.
Newer targeted therapies and immunotherapies can cause kidney injury by triggering inflammatory responses, such as acute interstitial nephritis. Radiation therapy can also affect the kidneys if they are located within the radiation field, such as during treatment for abdominal or paraspinal tumors. This complication is known as radiation nephritis, a condition that can have a long latency period, sometimes appearing months to years after the initial treatment.
Radiation nephritis causes progressive damage to the blood vessels and filtering cells (podocytes) within the kidney’s glomeruli. This leads to a gradual reduction in the glomerular filtration rate, often accompanied by high blood pressure and anemia. The risk is directly related to the total radiation dose and the volume of kidney tissue exposed.
Surgery and AKI
Major cancer surgery can also precipitate AKI, predominantly through prerenal causes. Acute blood loss and significant fluid shifts during complex operations can lead to hypovolemia, reducing blood flow to the kidneys. Major surgery also increases the risk of post-operative infections and sepsis, which is a leading cause of AKI due to systemic inflammation.
Monitoring and Maintaining Kidney Health During Cancer Care
Careful monitoring of kidney function is an integral part of high-quality cancer care, a discipline often referred to as onco-nephrology. Screening begins with blood tests to measure serum creatinine, a waste product whose concentration rises as kidney function declines. Because creatinine alone can be misleading, physicians often rely on the estimated glomerular filtration rate (eGFR) to accurately determine the functional capacity of the kidneys before administering nephrotoxic agents. Regular urinalysis is also performed to check for protein or blood in the urine, which signals damage to the filtration barrier.
Proactive supportive measures are employed to mitigate the risk of injury, especially when using highly nephrotoxic treatments. Aggressive intravenous hydration is a cornerstone of prevention for agents like cisplatin and in cases where tumor lysis syndrome is a risk, helping to flush the kidneys and prevent crystal formation. When kidney function is impaired, the dosage of chemotherapy drugs cleared by the kidneys must be carefully adjusted to prevent drug accumulation and excessive toxicity. This adjustment maximizes treatment effectiveness while protecting remaining kidney function.
For mechanical blockages, such as obstructive nephropathy, immediate intervention is necessary to relieve pressure and preserve function. This often involves placing a ureteral stent or a percutaneous nephrostomy tube to bypass the obstruction and allow urine to drain. When AKI develops, a consultation with a kidney specialist helps determine the cause and guide management, which may include specialized medications like bisphosphonates to quickly lower calcium levels in hypercalcemia. Timely intervention is paramount, as prolonged or severe damage can lead to chronic kidney disease or the need for dialysis.