ONCOLOGIC EMERGENCIES
Hyperuricemia
Overview
Hyperuricemia usually is a complication of rapid necrosis of tumor cells after
vigorous chemotherapy for lymphomas and leukemias. Hyperuricemia may be related to
increased uric acid production or to the tumor lysis syndrome associated with Burkitt’s
lymphoma. Uric acid crystals are deposited in the urinary tract, causing renal failure and
uremia. Patients with
hyperuricemia manifest with
nausea, vomiting, lethargy, and
oliguria. (LeMone, 2011)
Etiology and Risk Factors
Hyperuricemia occurs
most often in patients with hematologic disorders, particularly leukemias, high-grade
lymphomas, and myeloproliferative diseases (polycythemia vera). It may occur
secondary to treatment of the malignancy. (Escalante, 2015)
Assessment
Signs and Symptoms
Patients with clinical syndromes caused by hyperuricemia present with significant
elevations of serum uric acid levels. Gouty arthritis may be seen occasionally, but the
most significant complication is renal dysfunction, particularly acute renal failure.
Clinical symptoms associated with renal dysfunction vary depending on the degree of
dysfunction and the timing of its development. In patients with acute renal failure,
clinical symptoms may include abnormal mental status, nausea and vomiting, fluid
overload, pericarditis, and seizures. (Escalante, 2015)
LeMone, P., Burke, K. & Bauldoff, G. 2011. Medical-Surgical Nursing Fifth Edition. USA: Pearson. Pg. 377
Escalante, E. 2015. CancerNetwork. Oncologic Emergencies and Paraneoplastic Syndromes. Retrieved from:
http://www.cancernetwork.com/cancer-management/oncologic-emergencies-and-paraneoplastic-syndromes/page/0/5
ONCOLOGIC EMERGENCIES
Pathophysiology
Uric acid in the blood is saturated at 6.4-6.8 mg/dL at ambient conditions, with
the upper limit of solubility placed at 7 mg/dL. Urate is freely filtered at the glomerulus,
reabsorbed, secreted, and then again reabsorbed in the proximal tubule. The recent
cloning of certain urate transporters will facilitate the understanding of specific
mechanisms by which urate is handled in the kidney and small intestines.
A urate/anion exchanger (URAT1) has been identified in the brush-border
membrane of the kidneys and is inhibited by an angiotensin II receptor blocker,
losartan. [3] A human organic anion transporter (hOAT1) has been found to be inhibited
by both uricosuric drugs and antiuricosuric drugs, while another urate transporter (UAT)
has been found to facilitate urate efflux out of the cells. These transporters may account
for the reabsorption, secretion, and reabsorption pattern of renal handling of urate.
Urate secretion does appear to correlate with the serum urate concentration
because a small increase in the serum concentration results in a marked increase in urate
excretion.
Hyperuricemia may occur because of decreased excretion (underexcretors),
increased production (overproducers), or a combination of these two mechanisms. (Lohr,
2017)
Medical Management
Prophylactic measures
Prophylactic measures against the development of hyperuricemia should be
undertaken before initiation of chemotherapy. Drugs that increase serum urate levels or
produce acidic urine (eg, thiazides and salicylates) should be discontinued if possible.
Alkalinization of the urine should be initiated to maintain a urine pH greater than 7.
Usually, sodium bicarbonate solution (50 to 100 mmol/L) is added to intravenous fluids
and then adjusted so that an alkaline urine pH is maintained. The carbonic anhydrase
inhibitor acetazolamide may be used to increase the effects of alkalinization. It is
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-overview#a5
ONCOLOGIC EMERGENCIES
important to remember that alkalinization is secondary to the overall goal of decreasing
urinary uric acid concentration by increasing urine volume.
Allopurinol, a xanthine oxidase inhibitor, is the mainstay of drug treatment and
may be started 1 to 2 days before cytotoxic treatment. Dosages range from 300 to 600
mg/d, and therapy is usually continued for 1 to 2 weeks or until the danger of
hyperuricemia has passed.
Rasburicase (Elitek) is an antihyperuricemia drug. It has been approved by the
FDA for malignancy-associated hyperuricemia in pediatric patients but is also used in
adults. The usual pediatric dose is 0.15 or 0.2 mg/kg IV over 30 minutes for 5 days. The
usual adult dosage is 0.15 to 0.2 mg/kg/d, based on limited studies.
Nonsteroidal Anti-Inflammatory Drugs
Class Summary
Management of pain and inflammation in gout. Have analgesic, anti-inflammatory, and
antipyretic properties. Inhibit the enzyme cyclooxygenase, thus inhibiting biosynthesis of
prostaglandins and thromboxanes from arachidonic acid.
Indomethacin (Indochron E-R, Indocin)
Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and
glucuronide conjugation. Inhibits prostaglandin synthesis.
Discontinue 3-4 d following symptom resolution.
Xanthine Oxidase Inhibitors
Class Summary
Prevent gouty arthritis attacks and nephropathy. Used to treat hyperuricemia secondary to
diuretics or antineoplastics. Prevent recurrent uric acid nephrolithiasis.
Allopurinol (Zyloprim)
Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine.
Reduces synthesis of uric acid without disrupting biosynthesis of vital purines.
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-medication
ONCOLOGIC EMERGENCIES
Febuxostat (Uloric)
Xanthine oxidase inhibitor. Prevents uric acid production and lowers elevated serum uric
acid levels. Indicated for long-term management of hyperuricemia associated with gout.
Selective Uric acid Reabsorption Inhibitor (SURI)
Lesinurad (Zurampic)
Lesinurad is the first selective uric acid reabsorption inhibitor to be approved in the
United States. It acts by inhibiting the urate transporter, URAT1, which is responsible for
the majority of the renal reabsorption of uric acid. It also inhibits organic anion
transporter 4 (OAT4), a uric acid transporter associated with diuretic-induced
hyperuricemia. It is indicated in combination with a xanthine oxidase inhibitor for
hyperuricemia associated with gout in patients who have not achieved target serum uric
acid levels with a xanthine oxidase inhibitor alone.
Uricosuric Agents
Class Summary
Competitively inhibit reabsorption of uric acid in proximal renal tubule. This promotes
excretion of uric acid and lowers serum uric acid levels.
Probenecid (Benemid)
Used to treat and prevent hyperuricemia associated with gout and gouty arthritis.
Antigout Agents
Class Summary
Treatment of gouty arthritis attacks and prevention of their recurrence. Used in
management of familial Mediterranean fever.
Colchicine
Reduces formation of uric acid crystals in affected joint, thereby reducing amount of
acute inflammation and pain; also decreases uric acid levels in blood. Can be used in
combination with probenecid on long-term to prevent gout or can be used alone to treat
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-medication
ONCOLOGIC EMERGENCIES
pain and inflammation of acute gout attacks. Discontinue when pain of gout attack begins
to subside, when maximum dose is reached, or when GI symptoms (eg, nausea, vomiting,
diarrhea) indicate cellular poisoning. Decreases leukocyte motility and phagocytosis in
inflammatory responses.
Glucocorticoids
Class Summary
Have both anti-inflammatory (glucocorticoid) and salt retaining (mineralocorticoid)
properties. Glucocorticoids have profound and varied metabolic effects and modify the
body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Meticorten)
May decrease inflammation by reversing increased capillary permeability and
suppressing PMN activity.
Dexamethasone (Decadron, AK-Dex, Alba-Dex)
Decreases inflammation by suppressing migration of PMN leukocytes and reducing
capillary permeability.
Urate Oxidase Enzyme (Recombinant)
Class Summary
These agents facilitate conversion of urate to a more soluble product, allantoin.
Pegloticase (Krystexxa)
Pegylated uric acid–specific enzyme, which is a polyethylene glycol conjugate of
recombinant uricase. Achieves its therapeutic effect by catalyzing oxidation of uric acid
to allantoin, thereby lowering serum uric acid levels. Indicated for gout in adults
refractory to conventional therapy (ie, serum uric acid levels have failed to normalize and
signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at
maximum appropriate dose or xanthine oxidase inhibitors are contraindicated).
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-medication
ONCOLOGIC EMERGENCIES
Rasburicase (Elitek)
A recombinant form (derived from Saccharomyces cerevisiae -synthesized, Aspergillus
flavus) of the enzyme urate oxidase, which oxidizes uric acid to allantoin. Indicated for
treatment and prophylaxis of severe hyperuricemia associated with the treatment of
malignancy. Hyperuricemia causes a precipitant in the kidneys, which leads to acute renal
failure. Unlike uric acid, allantoin is soluble and easily excreted by the kidneys.
Elimination half-life is 18 h.
Alkalinizing Agent, Oral
Class Summary
These agents are used to raise the pH in the urine.
Potassium citrate (Citra K, Polycitra K)
Pleasant-tasting oral systemic alkalizer containing potassium citrate and citric acid in a
sugar-free base.
Each unit dose packet contains potassium citrate monohydrate 3300 mg and citric acid
monohydrate 1002 mg. Each unit dose packet, when reconstituted, supplies the same
amount of active ingredients as is contained in 15 mL (1 tablespoonful) Polycitra-K oral
solution and provides 30 mEq potassium ion and is equivalent to 30 mEq bicarbonate.
Absorbed and metabolized to potassium bicarbonate, thus acting as a systemic alkalizer.
Effects are essentially those of chlorides before absorption and those of bicarbonates
subsequently. Oxidation is virtually complete so that < 5% of the potassium citrate is
excreted in the urine unchanged. (Lohr, 2017)
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-medication
ONCOLOGIC EMERGENCIES
Diagnostic Tests
Laboratory Studies
Laboratory studies may include the following:
Serum uric acid
Complete blood cell count (CBC): Values may be abnormal in patients with
hemolytic anemia, hematologic malignancies, or lead poisoning.
Electrolytes, BUN, and serum creatinine values: These are abnormal in patients
with acidosis or renal disease.
Liver function tests: These are part of the general workup for patients with a
possible malignancy or metabolic disorders; in addition, the results are useful as a
baseline if allopurinol is used for treatment
Serum glucose level: This may be abnormal in patients with diabetes or glycogen
storage diseases.
Lipid profile: Results are abnormal in those with dyslipidemia.
Calcium and phosphate levels: This measurement is needed for the workup of
hyperparathyroidism, sarcoidosis, myeloma, and renal disease.
Thyroid-stimulating hormone level: Obtain this value to help rule out
hypothyroidism.
Urinary uric acid excretion
Fractional excretion of urate on a low-purine diet
Spot urine ratio of uric acid to creatinine
Urinary uric acid secretion
If uric acid levels are found to be persistently elevated, an estimation of total uric acid
excretion may be needed. The estimation of uric acid excretion is recommended in young
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-workup
ONCOLOGIC EMERGENCIES
males who are hyperuricemic, females who are premenopausal, people with a serum uric
acid value greater than 11 mg/dL, and patients with gout.
One protocol recommends obtaining two 24-hour urine collections for creatinine
clearance and uric acid excretion. The first collection is performed while patients are on
their usual diet and alcohol intake. At the end of the first 24-hour collection, serum
creatinine and urate levels are checked for an estimation of the creatinine clearance. The
patient then goes on a low-purine, alcohol-free diet for 6 days, with a repeat 24-hour
urine collection performed on the last day, followed by a serum creatinine and uric acid
evaluation.
Depending on the 24-hour urine uric acid levels before the purine-restricted diet and after
the purine-restricted diet, patients who are hyperuricemic can be categorized into the
following three groups:
High-purine intake - Prediet value greater than 6 mmol/d, postdiet value less than
4 mmol/d
Overproducers - Prediet value greater than 6 mmol/d, postdiet value greater than
4.5 mmol/d
Underexcretors - Prediet value less than 6 mmol/d, postdiet value less than 2
mmol/d
Fractional excretion of urate on a low-purine diet
This test should be used to investigate the degree of underexcretion in patients with
hyperuricemia or gout in patients for whom the cause cannot be determined.
The reference intervals for patients on a low-purine diet and normal renal function are as
follows:
Males - 7-9.5%
Females - 10-14%
Children - 15-22%
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-workup
ONCOLOGIC EMERGENCIES
Values less than the lower limits of the reference range indicate underexcretion. The
formula also circumvents any inaccuracy that may have occurred during urine collection.
Spot urine ratio of uric acid to creatinine
If a 24-hour urine collection is not possible, measure the ratio of uric acid to
creatinine from a spot urine collection. A ratio greater than 0.8 indicates overproduction.
The ratio also helps differentiate acute uric acid nephropathy from the
hyperuricemia that occurs secondary to renal failure. The ratio is greater than 0.9 in acute
uric acid nephropathy and usually less than 0.7 in hyperuricemia secondary to renal
insufficiency.
Imaging Studies
In patients with gout, radiographs may reveal evidence of joint swelling and
subcortical cysts. In patients with hyperuricemia and renal disease, a renal sonogram is an
important tool for kidney evaluation. Images from this study also may reveal the presence
of uric acid stones.
Procedures
Joint aspiration may be important in the diagnosis of acute gouty arthritis, in
which uric acid crystals are found to be negatively birefringent under polarized
microscopy. (Lohr, 2017)
Nursing Diagnosis
Acute pain
Chronic pain
Impaired physical mobility
Activity intolerance
Bathing/hygiene self-care deficit
Lohr, J. Medscape. 2017. Hyperuricemia. Retrieved from: http://emedicine.medscape.com/article/241767-workup
ONCOLOGIC EMERGENCIES
Nursing Management
1. Promote measures to prevent exacerbations
Urge the client to drink 2 to 3 L of fluid daily and to report any decrease in
urine output.
Teach the client about dietary modifications to limit foods high in purine
(e.g. organ meats, anchovies, sardines, shellfish, chocolate, meat extracts).
2. Provide measure to promote comfort and reduce pain.
Maintain strict bed rest for 24 hours after an attack.
Provide a bed cradle to keep bed linen off affected joints to help reduce
pain.
3. Administer prescribed medications, which may include nonsteroidal anti-
inflammatory drugs, uric acid synthesis inhibitors, and uricosuric agents.
Colchicine may be prescribed for acute attack and used in small doses for
prevention.
Nausea, vomiting, and diarrhea are toxic effects of colchicines and should
be reported to the health care provider.
(RNpedia, 2017)
RNpedia. 2017. Nursing Management. Retrieved from: https://www.rnpedia.com/nursing-notes/medical-surgical-
nursing-notes/gouty-arthritis-nursing-management/
