How does Tumor lysis syndrome cause AKI?
The primary mechanism of AKI in TLS is a crystal-induced nephropathy, usually due to uric acid. Glomerular filtration of uric acid followed by fluid reabsorption results in high concentrations within the tubular fluid, leading to the intratubular precipitation of uric acid crystals.
Uric acid crystallization is further promoted by volume depletion (nausea and vomiting, diarrhea, poor sodium intake) and low urinary pH (from metabolic acidosis, diuretics, and volume depletion).
The intratubular uric acid crystals cause tubular obstruction and may also cause tubular injury by stimulating an inflammatory response. Even if it does not crystalize, soluble uric acid may act as a kidney vasoconstrictor, exacerbating kidney hypoperfusion.
Uric acid is not the only nephrotoxin in TLS. Hyperphosphatemia may lead to the precipitation of calcium phosphate crystals, causing acute phosphate nephropathy. This is especially relevant where alkalinization of the urine is being used to protect against uric acid nephropathy, as alkaline urine promotes the precipitation of calcium phosphate stones.
