GOUT SCRIPT
ANTI-INFLAMMATORY PROPHYLAXIS DURING INITIATION OF
URATE-LOWERING THERAPY
Initiation of urate-lowering therapy can precipitate an acute gout
attack due to remodeling of urate crystal deposits in joints after rapid
lowering of urate concentrations. Prophylactic anti-inflammatory
therapy is often used to prevent such gout attacks.
• The ACR guidelines recommend low-dose oral colchicine (0.6 mg
twice daily) or low-dose NSAIDs (eg, naproxen 250 mg twice daily) as
first-line prophylactic therapies, with stronger evidence supporting
use of colchicine. For patients on long-term NSAID prophylaxis, a
proton pump inhibitor or other acid-suppressing therapy is indicated
to protect from NSAID-induced gastric problems.
• Low-dose corticosteroid therapy (eg, prednisone ≤10 mg/day) is an
alternative for patients with intolerance, contraindication, or lack of
response to first-line therapy. The potential severe adverse effects of
prolonged corticosteroid therapy preclude (prevents) their use as
first-line therapy.
- increased appetite – which may lead to weight gain if you
find it difficult to control what you eat, acne, rapid mood
swings and mood changes – becoming aggressive,
irritable and short-tempered with people, thin skin that
bruises easily, muscle weakness.
• Continue prophylaxis for at least 6 months or 3 months after
achieving target serum uric acid, whichever is longer. For patients
with one or more tophi, continue prophylactic therapy for 6 months
after achieving the serum urate target
NEPHROLITHIASIS
With nephrolithiasis, “nephro-” refers to the kidneys, and “-lithiasis”
means stone, so nephrolithiasis means kidney stones, sometimes also
referred to as renal calculi or urolithiasis.
Kidney stones form when solutes in the urine precipitate out and
crystalize, and although these most commonly form in the kidneys
themselves, they can also form in the ureters, the bladder, or the
urethra.
Now, urine’s a combination of water, which acts as a solvent, and all
sorts of particles, or solutes.
In general, when certain solutes become too concentrated in the
solvent, they become supersaturated. Urinary supersaturation of
certain solutes results in precipitation out of the solution and
formation of crystals.
More solutes can deposit and over time it builds up a crystalline
structure. This can happen if there’s an increase in the solute, or a
decrease in the solvent, as would be the case with dehydration.
In addition, there are substances like magnesium and citrate that
inhibit crystal growth and aggregation, preventing kidney stones from
forming in the first place.
- In the majority of cases, the inorganic precipitate is calcium
oxalate, formed by a positively charged calcium ion binding to
a negatively charged oxalate ion, which results in a black or
dark brown colored stone that is radio-opaque on an Xray,
meaning that it shows up as a white spot.
At a physiologic pH, uric acid loses a proton and becomes a urate ion,
which then binds sodium, forming monosodium urate which
crystallizes and ultimately forms uric acid stones.
Since uric acid is a breakdown product of purines, a very common
reason for high levels of uric acid is consuming lots of purines. Purine-
rich foods include shellfish, anchovies, red meat or organ meat.
There are some rare stones made of xanthine, which, just like uric
acid, is a byproduct of purine breakdown. These stones, also like uric
acid stones, are red-brown in color and radiolucent under an X-ray.
The primary treatments are to alkalinize (citrate or bicarbonate) and
dilute (large water intake) the urine.
Treatment or management includes hydrating an individual to
reverse the process of precipitation.
Alkalinizing agents should be used with the objective of making the
urine less acidic. Urine pH should be maintained at 6 to 6.5 this is
because in this pH range, up to 85% of uric acid will be in the form of
the soluble urate ion. Soluble urate ion will be easily excreted by the
kidneys.
Reduction of urine acidity is usually accomplished by the
administration of potassium bicarbonate or potassium citrate 60 to
80 mEq/day. Also, these medications might be given, to help reduce
pain, reduce stone formation, like potassium citrate, and to help
stones pass through
- like alpha adrenergic blockers and calcium channel blockers
- Potassium citrate is preferred because it can also reduce
urinary calcium, and it provides citrate as a lithoprotective
element.
- Also shockwave lithotripsy might be used, which is a
noninvasive treatment that uses high-intensity acoustic pulses
that travel through the body to break up the kidney stones.
- Finally, surgery and stent placement might be needed for
larger stones.
Acetazolamide, a carbonic anhydrase inhibitor, produces rapid and
effective urinary alkalinization and sometimes is used in conjunction
with alkali therapy. When a 250-mg dose of acetazolamide is given at
bedtime, the excretion of acidic urine in the early morning hours is
avoided. The medication works to excrete bicarbonate. Doing so
alkalizes the urine as there is greater bicarbonate in the urine. As a
result, the blood is more acidic, given that the bicarbonate has been
excreted.
The usual tachyphylaxis (rapid tolerance) to this drug is obviated
(removed or prevented) by a daily repletion (act of replenishing) dose
of bicarbonate.
Patients are still advised to avoid foods rich in purine and to limit
protein to no more than 90 g/day. Such a diet is still palatable and
reduces appreciably the amount of uric acid in the urine.
The mainstay of drug therapy for recurrent uric acid nephrolithiasis is
xanthine oxidase inhibitors (allopurinol and febuxostat). They are
effective in reducing both serum and urinary uric acid concentrations,
thus preventing the formation of calculi. Xanthine oxidase inhibitors
are recommended as prophylactic treatment for patients who will
receive cytotoxic agents for the treatment of lymphoma or leukemia.
The marked increase in uric acid production associated with cytolysis
of a neoplasm predisposes a patient to the development of uric acid
nephrolithiasis.
URIC ACID LOWERING IN THE ABSENCE OF GOUT
ASYMPTOMATIC HYPERURICEMIA
The purported benefits using drug therapy for the treatment of
asymptomatic hyperuricemia include prevention of acute gouty
arthritis, tophi formation, nephrolithiasis, and chronic urate
nephropathy. Specifically, the prevention of urate nephropathy might
be a stronger indication because it is irreversible even with proper
treatment. Kidney disease associated with hyperuricemia is very rare
in the absence of concurrent hypertension and atherosclerosis.

URIC ACID AND CARDIOVASCULAR RISK
The relationship between elevated serum urate concentrations and
cardiovascular disease is controversial. In observational studies,
hyperuricemia has been shown to be a risk factor for ischemic heart
disease. However, hyperuricemia is also associated with other known
risk factors for cardiovascular disease, such as diabetes mellitus,
dyslipidemia, and hypertension.
PHARMACOTHERAPY CONSIDERATIONS
Allopurinol hypersensitivity syndrome is perhaps the most concerning
adverse effect of all potential side effects associated with gout
therapies, given the high-mortality rate associated with this reaction.
As such, it would be ideal if patients at high risk for developing this
syndrome could be screened for and, consequently, guided to
alternative therapy.
Korean patients with chronic kidney disease (stage 3 or worse), Han
Chinese patients, and Thai patients have been identified as being at
increased risk for allopuri- nol hypersensitivity syndrome if found to
have a specific genotype (HLA-B*5801 positive). The ACR guidelines
recommend that HLA-B*5801 testing be considered before
allopurinol initiation in these specific subpopulations; for those found
to be positive, alter- native therapy should be used.
Certain comorbidities may warrant dose adjustment of some gout
therapies or, in certain instances, complete avoidance of certain
medications. For example, patients with impaired kidney function
should, in general, avoid NSAID therapy and must receive colchicine
at reduced doses. Patients with GI disease should also avoid NSAID
therapy and may not be able to tolerate colchicine therapy and,
therefore, may find most success with corticosteroid therapy.
EVALUATION OF THERAPEUTIC OUTCOMES
Check the serum uric acid level in patients suspected of having an
acute gout attack, particularly if it is not the first attack, and a decision
is to be made about starting prophylaxis. However, acute gout can
occur with normal serum uric acid concentrations.
• Monitor patients with acute gout for symptomatic relief of joint
pain as well as potential adverse effects and drug interactions related
to drug therapy. Acute pain of an initial gout attack should begin to
ease within about 8 hours of treatment initiation. Complete
resolution of pain, erythema, and inflammation usually occurs within
48–72 hours.
• For patients receiving urate-lowering therapy, obtain baseline
assessment of kidney function, hepatic enzymes, complete blood
count, and electrolytes. Recheck the tests every 6–12 months in
patients receiving long-term treatment.
• During titration of urate-lowering therapy, monitor serum uric acid
every 2–5 weeks; after the urate target is achieved, monitor uric acid
every 6 months.
• Because of the high rates of comorbidities associated with gout
(diabetes, chronic kidney disease, hypertension, obesity, myocardial
infarction, heart failure, and stroke), elevated serum uric acid
concentrations or gout should prompt evaluation for cardiovascular
disease and the need for appropriate risk reduction measures.
Clinicians should also look for possible correctable causes of
hyperuricemia (eg, medications, obesity, malignancy, and alcohol
abuse