Chapter 46 - Radiological Contrast Agents and Radiopharmaceuticals
- Hyperuricemia[4] and hyperuricosuria. Massive cell death and nuclear breakdown generates large quantities of nucleic acids. Of these, the purines (adenine and guanine) are converted to uric acid via the purine degradation pathway and excreted in the urine. However, at the high concentrations of uric acid generated by tumor lysis, uric acid is apt to precipitate as monosodium urate crystals.
Acute uric acid nephropathy (AUAN) due to hyperuricosuria has been a dominant cause of acute kidney failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.
- Hyperkalemia. Potassium is mainly an intracellular ion. High turnover of tumor cells leads to spill of potassium into the blood. Symptoms usually do not manifest until levels are high (> 7 mmol/L) [normal 3.5–5.0 mmol/L] and they include
- cardiac conduction abnormalities (can be fatal)
- severe muscle weakness or paralysis
- Hyperphosphatemia. Like potassium, phosphates are also predominantly intracellular. Hyperphosphatemia causes acute kidney failure in tumor lysis syndrome, because of deposition of calcium phosphate crystals in the kidney parenchyma.
- Hypocalcemia. Because of the hyperphosphatemia, calcium is precipitated to form calcium phosphate, leading to hypocalcemia. Symptoms of hypocalcemia include (but are not limited to):
- tetany
- sudden mental incapacity, including emotional lability
- Parkinsonian (extrapyramidal) movement disorders
- papilledema
- myopathy
- Hyperuricemia[4] and hyperuricosuria. Massive cell death and nuclear breakdown generates large quantities of nucleic acids. Of these, the purines (adenine and guanine) are converted to uric acid via the purine degradation pathway and excreted in the urine. However, at the high concentrations of uric acid generated by tumor lysis, uric acid is apt to precipitate as monosodium urate crystals.
Acute uric acid nephropathy (AUAN) due to hyperuricosuria has been a dominant cause of acute kidney failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.
- Lactic acidosis.[5][6]
- Pretreatment spontaneous tumor lysis syndrome. This entity is associated with acute kidney failure due to uric acid nephropathy prior to the institution of chemotherapy and is largely associated with lymphoma and leukemia. The important distinction between this syndrome and the post-chemotherapy syndrome is that spontaneous TLS is not associated with hyperphosphatemia. One suggestion for the reason of this is that the high cell turnover rate leads to high uric acid levels through nucleobase turnover but the tumor reuses the released phosphate for growth of new tumor cells. In post-chemotherapy TLS, tumor cells are destroyed and no new tumor cells are being synthesized.[citation needed] TLS is most common during cytotoxic treatment of hematologic neoplasms.[7]
The most common tumors associated with this syndrome are poorly differentiated lymphomas (such as Burkitt's lymphoma), other Non-Hodgkin Lymphomas (NHL), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML).[3] Other cancers (such as melanoma) have also been associated with TLS but are less common.
Lyphoma recos
TLS can be triggered in cancer patients by steroid treatment alone, and sometimes without any treatment—in this case the condition is referred to as "spontaneous tumor lysis syndrome".[7][9]
TLS is most common during cytotoxic treatment of hematologic neoplasms.[7]
In 2011, Howard proposed a refinement of the standard Cairo-Bishop definition of TLS accounting for 2 limitations:[11]
- Two or more electrolyte laboratory abnormalities must be present simultaneously to be considered related to TLS. In fact, some patients may present with one abnormality, but later another one may develop that is unrelated to the TLS (e.g., hypocalcemia associated with sepsis).
- A 25% change from baseline should not be considered a criterion since such increases are rarely clinically important unless the value is already outside the normal range.
Moreover, any symptomatic hypocalcemia should constitute clinical TLS.
People about to receive chemotherapy for a cancer with a high cell turnover rate, especially lymphomas and leukemias, should receive prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor, which inhibits uric acid production) as well as adequate IV hydration to maintain high urine output (> 2.5 L/day). Allopurinol works by preventing the formation of uric acid following tumor cell lysis.[7]
Rasburicase is an alternative to allopurinol[12][13] and is reserved for people who are high-risk in developing TLS, or when xanthine oxidase inhibition is contraindicated (taking 6-MP or azathioprine). It is a synthetic urate oxidase enzyme and acts by degrading uric acid.[14] However, it's not clear if it results in any important benefits as of 2014.[2]Alkalization of the urine with acetazolamide or sodium bicarbonate is controversial. Routine alkalization of urine above pH of 7.0 is not recommended. Alkalization is also not required if uricase is used.[citation needed]
Treatment[edit]
Treatment is first targeted at the specific metabolic disorder.
Acute kidney failure prior to chemotherapy. Since the major cause of acute kidney failure in this setting is uric acid build-up, therapy consists of rasburicase to wash out excessive uric acid crystals as well as a loop diuretic and fluids. Sodium bicarbonate should not be given at this time. If the patient does not respond, hemodialysis may be instituted, which is very efficient in removing uric acid, with plasma uric acid levels falling about 50% with each six-hour treatment.[citation needed]
Acute kidney failure after chemotherapy. The major cause of acute kidney failure in this setting is hyperphosphatemia, and the main therapeutic means is hemodialysis. Forms of hemodialysis used include continuous arteriovenous hemodialysis (CAVHD), continuous venovenous hemofiltration (CVVH), or continuous venovenous hemodialysis (CVVHD).
https://en.wikipedia.org/wiki/Tumor_lysis_syndrome
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