Hyperphosphatemia in TLS

Q: What's the cause of hyperphosphatemia in tumor lysis syndrome (TLS)?

Answer: The concentration of phosphorus in malignant cells is up to four times higher than in normal cells.

Rapid tumor breakdown during chemotherapy leads to hyperphosphatemia due to the above reason. The significant domino effect is hypocalcemia, causing tetany and/or seizures. 

When the product of calcium concentration and phosphate concentration, known as the calcium phosphate product, exceeds 60 mg2/dL2, there is a high risk of calcium phosphate precipitation in the renal tubules, leading to acute kidney injury (AKI). The same precipitation in cardiac muscles causes arrhythmias. Renal replacement therapy should be highly considered once the calcium phosphate product is ≥70 mg2/dL2. 

In the past, hyperuricemia was the leading cause of AKI in TLS. Since the advent of effective hypouricemic agents, calcium phosphate deposition, i.e., nephrocalcinosis, has become the leading cause of acute kidney injury in TLS.

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#nepheology

#electrolytes

References:

1. Kikuchi S, Muro M, Kamihara Y, Wada A, Murakami J, Nabe Y, Minemura T, Sato T. Massive hyperphosphatemia in clinical tumor lysis syndrome during prophylactic rasburicase use: risk factors and treatment options. Int Cancer Conf J. 2022 Oct 28;12(1):69-74. doi: 10.1007/s13691-022-00580-9. PMID: 36605847; PMCID: PMC9807691.

2. Amaechi PK, Jenssen F, Krishnasami Z, Achanti A, Fülöp T. Excessive elevation of serum phosphate during tumor lysis syndrome: Lessons from a particularly challenging case. Clin Nephrol Case Stud. 2021 Apr 16;9:39-44. doi: 10.5414/CNCS110086. PMID: 33884255; PMCID: PMC8056318.

3. Lindsay AB, Levy NJ, McAndrew ML. Tumor Lysis Syndrome. Emerg Med Clin North Am. 2025 Aug;43(3):453-461. doi: 10.1016/j.emc.2025.04.002. Epub 2025 May 12. PMID: 40610062.