Chemotherapy uses powerful drugs to destroy rapidly dividing cancer cells throughout the body. While effective, this treatment can cause unintended side effects in other organ systems, including the kidneys. Kidney stones, or nephrolithiasis, are a potential complication arising from metabolic disturbances caused by cancer therapy. These solid masses form when crystallized substances build up in the urinary tract, causing severe pain and obstruction. Understanding the underlying mechanisms is important for mitigating this risk.
Mechanisms Linking Chemotherapy to Kidney Stone Risk
The primary mechanism linking chemotherapy to kidney stone formation is Tumor Lysis Syndrome (TLS). TLS occurs when chemotherapy rapidly breaks down a large volume of cancer cells, causing their intracellular contents to spill into the bloodstream. These contents include nucleic acids, which are metabolized into high levels of uric acid, a condition called hyperuricemia.
Uric acid has low solubility, especially in an acidic environment, leading to its precipitation within the renal tubules. These uric acid crystals aggregate to form stones, which can obstruct urine flow and lead to acute kidney injury. This process is a significant concern, particularly in patients with large, fast-growing tumors that are highly sensitive to treatment.
Chemotherapy’s common side effects also contribute to stone formation through dehydration and reduced urine volume. Nausea, vomiting, and diarrhea are frequent complications, making it difficult for patients to maintain adequate fluid intake. When dehydrated, the urine becomes highly concentrated, causing stone-forming substances like uric acid and calcium salts to crystallize more easily.
The balance of acidity or alkalinity in the urine, measured by its pH, also plays a role in determining stone risk. Uric acid crystals precipitate readily when the urine is acidic. However, certain chemotherapy agents or supportive care medications can shift the urine to an alkaline state.
An alkaline urine environment, while helpful for dissolving uric acid stones, can favor the precipitation of other stone types, such as calcium phosphate. High solute concentration from TLS often combines with low urine volume from dehydration to significantly increase the overall risk of stone development.
Specific Chemotherapy Drugs Implicated in Stone Formation
Some chemotherapy drugs carry an intrinsic risk of stone formation by precipitating directly in the kidneys or causing specific electrolyte imbalances. High-dose methotrexate, used for certain leukemias and lymphomas, is one such drug. The drug or its metabolic byproducts can precipitate within the renal tubules, leading to crystal-induced nephrotoxicity.
This precipitation causes direct kidney damage that impairs renal function and creates an environment conducive to stone growth. To prevent this, medical teams employ strict hydration and urine alkalinization protocols when administering high doses of methotrexate. Nephrotoxicity is reported in a significant percentage of patients, underscoring the need for careful monitoring.
Platinum-based chemotherapy drugs, such as cisplatin, are well-known for their potential to cause kidney toxicity. Cisplatin affects the renal tubules, leading to acute tubular injury in a substantial number of patients. This damage impairs the kidney’s ability to manage electrolytes, which indirectly leads to calcium and magnesium imbalances in the urine.
The resulting hypercalciuria, or excessive calcium excretion, increases the concentration of calcium available to form stones. The risk of kidney damage from these agents is cumulative and depends on the total dose administered over time.
Prevention and Management of Stones During Treatment
Aggressive hydration is the cornerstone of prevention, especially in high-risk patients. This involves administering large volumes of intravenous fluids before, during, and after chemotherapy. The goal is to maintain a high urine output, often targeting at least 100 milliliters per hour, to effectively dilute and flush out stone-forming substances.
Controlling hyperuricemia is another primary focus, utilizing medications to manage uric acid levels. Allopurinol is commonly prescribed to block the production of new uric acid by inhibiting the enzyme xanthine oxidase. This medication is typically started a few days before chemotherapy begins to establish a protective level.
For patients at the highest risk of Tumor Lysis Syndrome, rasburicase may be used instead. Rasburicase is an enzyme that rapidly converts existing uric acid into allantoin, a more water-soluble substance easily excreted by the kidneys. Patients are usually screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency before administration, as rasburicase can cause severe adverse reactions.
Patients undergoing chemotherapy must be aware of common stone symptoms, which can sometimes be mistaken for general side effects. Symptoms necessitating immediate medical consultation include sharp pain in the flank or side, blood in the urine (hematuria), and a significant decrease in urine output. Rapid recognition and treatment of these signs are important to prevent kidney function from deteriorating.
If a stone does form, standard treatment protocols are adapted to the patient’s active cancer treatment plan. Management typically includes pain control and continued aggressive hydration. Depending on the stone’s size and location, procedures like lithotripsy or surgical removal may be necessary to relieve obstruction and preserve kidney function.