When cancer cells lyse, they release potassium, phosphorus, and nucleic acids, which are metabolized into hypoxanthine, then xanthine, and finally uric acid, an end product in humans ().12
Hyperkalemia can cause serious — and occasionally fatal — dysrhythmias. Hyperphosphatemia can cause secondary hypocalcemia, leading to neuromuscular irritability (tetany), dysrhythmia, and seizure, and can also precipitate as calcium phosphate crystals in various organs (e.g., the kidneys, where these crystals can cause acute kidney injury).13
Uric acid can induce acute kidney injury not only by intrarenal crystallization but also by crystal-independent mechanisms, such as renal vaso-constriction, impaired autoregulation, decreased renal blood flow, oxidation, and inflammation.14-16
Tumor lysis also releases cytokines that cause a systemic inflammatory response syndrome and often multiorgan failure.17-19
Lysis of Tumor Cells and the Release of DNA, Phosphate, Potassium, and Cytokines
The tumor lysis syndrome occurs when more potassium, phosphorus, nucleic acids, and cytokines are released during cell lysis than the body’s homeostatic mechanisms can deal with. Renal excretion is the primary means of clearing urate, xanthine, and phosphate, which can precipitate in any part of the renal collecting system. The ability of kidneys to excrete these solutes makes clinical tumor lysis syndrome unlikely without the previous development of nephropathy and a consequent inability to excrete solutes quickly enough to cope with the metabolic load.
Crystal-induced tissue injury occurs in the tumor lysis syndrome when calcium phosphate, uric acid, and xanthine precipitate in renal tubules and cause inflammation and obstruction ().20,23
A high level of solutes, low solubility, slow urine flow, and high levels of cocrystallizing substances favor crystal formation and increase the severity of the tumor lysis syndrome.24-26
High levels of both uric acid and phosphate render patients with the tumor lysis syndrome at particularly high risk for crystal-associated acute kidney injury, because uric acid precipitates readily in the presence of calcium phosphate, and calcium phosphate precipitates readily in the presence of uric acid. Also, higher urine pH increases the solubility of uric acid but decreases that of calcium phosphate. In patients treated with allopurinol, the accumulation of xanthine, which is a precursor of uric acid and has low solubility regardless of urine pH, can lead to xanthine nephropathy or urolithiasis ().20,27
Crystals of Uric Acid, Calcium Phosphate, and Calcium Oxalate
Calcium phosphate can precipitate throughout the body (). The risk of ectopic calcification is particularly high among patients who receive intravenous calcium.13
When calcium phosphate precipitates in the cardiac conducting system, serious, possibly fatal, dysrhythmias can occur. Acute kidney injury developed in our patient as a result of the precipitation of uric acid crystals and calcium phosphate crystals and was exacerbated by dehydration and acidosis that developed because the tumor lysis syndrome had not been suspected and no supportive care was provided.