Statistical modeling in pharmaceutical research and development.
GOUTY ARTHRITIS ASSOCIATED WITH KIDNEY FAILURE
1. TERNOPIL STATE MEDICAL UNIVERSITY
UKRAINE
DEPARTMENT OF INTERNAL MEDICINE
(HEMATOLOGY)
A PRESENTATION ON GOUTY
ARTHRITIS ASSOCIATED WITH KIDNEY
FAILURE BY
DR JOSEPH UCHENNA VICTOR
GROUP 5 4TH COURSE
4. INTRODUCTION
Gouty arthritis refers to a form of arthritis caused by deposits of
needle-like crystals of uric acid, usually strikes a single joint,
most commonly the big toe (about 75% of people are affected
at least once), however, it can also affect the
foot (instep/heel), ankles, knees, wrists, fingers, elbows
Gouty arthritis is rare in children and young adults. Men are
more likely to develop gouty arthritis than women.
The main cause of development of gout is deposition of uric
acid crystals in the synovial fluid and synovial lining of joints.
5. Gout may occur alone (primary gout) or may be associated with
other medical conditions or medications (secondary gout).
Gout results when crystals of uric acid form in tissues of the
body. Gout is characterized by an overload of uric acid in the
body and recurring attacks of joint inflammation (arthritis).
Chronic gout can lead not only arthritis, but hard lumps of uric
acid in and around the joints, decreased kidney function, and
kidney stones. Gouty arthritis is usually an extremely painful
attack with a rapid onset of joint inflammation. The inflammation
is precipitated by the deposition of uric acid crystals in the lining
of the joint (synovial lining) and the fluid within the joint. Intense
joint inflammation occurs when white blood cells engulf the
crystals of uric acid and release chemicals that promote
inflammation. The resulting inflammation causes pain, heat, and
redness of the joint.
6. CAUSES SYMPTOM RISk FACTOR FOR (Gouty
Arthritis)
This disease causes the inflammation, pain, redness and
tenderness of the joints of big toe, ankles, knees, feet, wrists
and hands. Higher levels of uric acid, obesity, exposure to lead
in the environment, high intake of food containing purines,
high alcohol intake and abnormal kidney function are the major
risk factors for gout (gouty arthritis).
People with impaired excretion of uric acid or increased
production of uric acid have high risk for development of gout.
Elevated uric acid levels may be associated with obesity, age,
diabetes mellitus, type IV hyperlipidaemia, hypertension and
coronary heart diseases. Besides this, certain conditions like
joint injury, dehydration, excessive dining, fever, recent surgery
and heavy alcohol intake are considered as the risk factors for
gout (gouty arthritis
7. Patients with impaired renal function or kidney failure are more
susceptible to gout. Uric acid present in normal amounts gets
dissolved in the blood and easily passes through the kidneys. But
due to kidney dysfunction, there is increase in uric acid levels in
the blood which may result in formation of crystals of uric acid.
These uric acid crystals get accumulated in the synovial fluid and
lining and cause inflammation of joints.
A person with medications like aspirin, levodopa and diuretics is
more prone to gout as these medications can interfere with the
ability of body to remove uric acid. Besides that, the medications
like cyclosporine used to suppress the immune system of the
body after organ transplant, can increase the risk for developing
this disease.
Intake of foods containing large amounts of uric acid such as red
meats and internal organs like kidneys and liver, anchovies and
some shellfish can lead to raised levels of uric acid and
development of gout. Excessive intake of alcohol is associated
with gout in young people.
8. Certain medical conditions like rapid weight loss, chronic kidney
disease, high blood pressure, hypothyroidism, surgery and
conditions like multiple myeloma, psoriasis, tumors or hemolytic
anemia are also significant risk factors for gout (gouty arthritis).
People with Lesch-Nyhan syndrome or Kelley-Seegmiller
syndrome may have deficiency of enzyme that controls the uric
acid levels. Such people have a greater risk of developing gouty
arthritis.
In addition to that, heredity, age and gender significantly
contribute in development of gout. Usually, men are commonly
affected by gout than women. Men in the middle age with high
blood pressure, obesity, heavy alcohol intake and unhealthy
cholesterol levels are more susceptible to this disorder.
9. DIAGNOSIS
Joint aspiration: This is the most important diagnostic
test. It is the ultimate method of being certain of a
diagnosis of gouty arthritis, as opposed to other causes
such as an infection in the joint.
Blood tests:
Your doctor may obtain a blood sample to look at your
cell counts, uric acid levels, kidney function, etc.
Radiographs:
X-rays are primarily used to assess underlying joint
damage, especially in those who have had multiple
episodes of gouty arthritis.
10. DIFFERENTIAL DIAGNOSIS
Diagnostic Considerations
The history and physical examination alone cannot reliably
determine the cause of new-onset acute monoarticular arthritis.
Septic arthritis, gout, and pseudogout can present in very similar
ways.
Certain clinical presentations are so characteristic of gout that
attempts have been made to accurately diagnose or exclude gout
without joint aspiration.
Male sex
Previous arthritis attack
Onset within 1 day
Joint redness
First metatarsophalangeal joint involvement
Hypertension or one or more cardiovascular diseases
A serum uric acid level of more than 5.88 mg/dL
11. Arthritis as a Manifestation of Systemic Disease
Bursitis
Cellulitis
Chondrocalcinosis
Hyperparathyroidism
Nephrolithiasis
Paronychia
Rheumatoid Arthritis
Septic Arthritis
Tenosynovitis
12. TREATMENT
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Examples include indomethacin(Indocin), ibuprofen (Advil),
andnaproxen (Aleve). Newer drugs such ascelecoxib (Celebrex)
can also be used. Aspirin should not be used for this condition.
High doses of anti-inflammatory medications are needed to
control the inflammation and can be tapered off within a couple
of weeks.
13. Colchicine (Colcry)
This medication is given in two different ways, either to treat the
acute attack of arthritis or to prevent recurring attacks
To treat the hot, swollen joint, colchicine is given rapidly
(generally, two tablets at once followed by another tablet an
hour later).
To help prevent an attack from coming back, colchicine can be
given once or twice a day. While the chronic use of colchicine
can reduce the attacks of gout, it does not prevent the
accumulation of uric acid that can lead to joint damage even
without attacks of hot, swollen joints.
Tell your doctor if you have any problems with your kidney or
liver function.
14. Corticosteroids
Corticosteroids such as prednisone (Meticorten, Sterapred,
Sterapred DS) are generally given when your doctor feels this is
a safer approach than using NSAIDs.
When given by mouth, high-dose corticosteroids are used
initially and tapered off within a couple of weeks. It is important
to take these medications as prescribed to avoid problems.
Some complications with the short-term use of corticosteroids
include altered mood, elevated blood pressure, and problems
with control of glucose in patients with diabetes
Corticosteroids can also be injected into the swollen joint.
Resting the joint temporarily, after it is injected with steroids,
can be helpful.
Occasionally, corticosteroids or a related
compound, corticotropin(ACTH), can also be injected into the
muscle or given intravenously.
15. CONCLUSION
In this study a high prevalence of CKD was observed among gout
patients. Serum uric acid goal attainment was low among patients
treated with allopurinol, and poorest among those with CKD. The
findings suggest that poor outcomes among gout patients with CKD
are partly due to clinicians' reluctance to prescribe higher doses of
allopurinol to patients with impaired renal function. The benefits and
risks of allopurinol treatment must be weighed carefully in patients
with CKD, and alternate treatment approaches are needed to improve
the prognosis of these patients. Future research should address at
least three additional issues: (1) the role of non-oxypurinol
metabolites of allopurinol in efficacy and toxicity, (2) more
sophisticated pharmacogenomics-based studies of allopurinol dosing
in the presence of CKD, and (3) development of urate-lowering drugs
that are not renally cleared. Additionally, our results suggest a need to
raise awareness among physicians regarding the importance of
titrating therapy to reach uric acid goals.