Lifestyle Change in Patients with Hyperuricemia Subtitle The amount of urate in the body depends on the balance between dietary intake synthesis and excretion Hyperuricemia ID: 930041
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Slide1
In The Name Of GOD
DR PARIN HEDAYATI
Slide2Lifestyle Change in Patients with
Hyperuricemia
Subtitle
Slide3The amount of
urate
in the body,
depends
on the balance between dietary intake, synthesis,
and excretion. Hyperuricemia results from the overproduction of uric acid (10%), underexcretion of uric acid (90%), or often a combination of the two.
3
Slide4Uric
Acid Metabolism
Uric acid is the final product of
purine
metabolism in humans.
Purines are components of nucleosides.Purine nucleosides (adenosine and guanine) are used in the creation of other metabolically important factors as well, such as
ATP,
the methyl
donor, and NADH; an important cofactor in energy production and antioxidation
4
Slide5Excess
purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys.
The
purines are first converted into the
uric acid
.5
Slide6The levels of uric acid in the blood depend on two factors
The
first is the rate of uric acid synthesis in the liver
.
Since uric acid results from purine degradation, its levels are influenced by both the amount of purines synthesized in the body, as well as the amounts of purines absorbed from the diet .6
Slide7…The levels of uric acid in the blood depend on two factors
The second is the rate of uric acid excretion from the kidneys. Excretion has the greatest effect on blood uric acid levels, with about 90% of
hyperuricemia
cases attributed to impaired renal excretion
.
Impaired excretion is most often due to abnormalities in the kidney urate transporter (called URAT1) or organic ion transporter (OAT), both of which control the movement of uric acid out of proximal kidney tubules and into urine.
7
Slide8One of the most intriguing aspects of uric acid is that although it appears to be a "waste product" of purine metabolism, only about 10% of the uric acid that enters a normal human kidney is excreted from the body
.
The
reason for this is likely due to the role or uric acid as one of the most important antioxidants in body fluids, responsible for the neutralization of over 50% of the free radicals in the blood stream
.
8
Slide9uric acid has a principle role in protecting high-oxygen tissues (like the brain) from damage, and low blood uric acid levels have been associated with the progression or increased risk of several neurological disorders, including Amyotrophic Lateral Sclerosis
, Multiple
sclerosis ,
and
Huntington's
,Parkinson's ,and Alzheimer's diseases .9
Slide10Uric acid is a metabolic "waste product" with poor solubility in body fluids, yet its potential role as a primary antioxidant in body fluids suggests that it should be kept at sufficient levels in the blood
.
Clearly, these diametric properties of uric acid define a range for normal blood uric acid levels
.
Commonly, the upper limit of this range is taken as 8.6 mg/dl in men and 7.1 mg/dl in women, Uric acid levels above this limit are considered as hyperuricemia.
10
Slide11Hyperuricemia
is a primary risk factor for the development of gout, although it is likely that many
hyperuricemic
individuals will not develop symptoms.
The
risk of a gout attack increases with blood uric acid. 11
Slide12Hyperuricemia
without symptoms (asymptomatic
hyperuricemia
) is also a risk factor for other diseases
.
Although patients with asymptomatic hyperuricemic may never experience the symptoms of a gout attack, ultrasound studies have revealed that up to one-third may have urate deposits and evidence of inflammation in their joints and surrounding soft tissues .
12
Slide13As local serum uric acid concentrations rise above their limit of solubility, monosodium
urate
can begin to precipitate out of the blood, forming needle-like crystals preferentially in cartilage and fibrous tissues. Here, the crystals may reside for years without causing problems
.
Urate
crystals within tissues have two fates; they can re-dissolve in body fluids and reenter circulation, or may be "shed" from the tissue. Shed monosodium urate crystals can enter nearby joint spaces or bursa provide cushioning between tendons and bones where they are quickly engulfed by immune cells. This activates a localized inflammatory response, leading to the characteristic arthritis of gout
.
13
Slide14Although
hyperuricemia
is most often associated with gout, elevated blood levels of uric acid have also been associated with other diseases.
Hyperuricemia
and gout are both risk factors
for
urolithiasis
. Both conditions increase the
risk of
forming not only uric acid stones, but also the more common calcium oxalate stones.
14
Slide15Deposits of monosodium
urate
crystals in kidney tissues can result in kidney damage (nephropathy), either acutely by formation of crystals within the tubules of the kidney, or through a chronic inflammatory response to
urate
deposits in other tissues of the kidney .
15
Slide16Hyperuricemia
is a risk factor for
cardiovascular diseases
in high risk
groups
It is often seen in patients with hypertension; high blood pressure has long been thought to contribute to elevated blood uric acid, possibly due to reduced blood flow to the kidneys and lower urate excretion .This effect was more pronounced in women and young adults. Lowering of uric acid levels in hyperuricemic, hypertensive adolescents reduced their blood pressure as well
.
Ironically
, the increased risk of cardiovascular diseases associated with hyperuricemia may be due to increases in oxidative stress: xanthine oxidase, the enzyme that synthesizes uric acid, also produces free radicals in the process
16
Slide17Hyperuricemia
is an integral part of
metabolic syndrome
, and
epidemiological studies have demonstrated that elevated uric acid levels substantially increase metabolic syndrome risk (and vice versa)
.Data from the Multiple Risk Factor Intervention Trial (MRFIT) showed that hyperuricemia was associated with increased risk of type 2 diabetes, and that male patients with gout had a 41% increased risk for the disease.
17
Slide18The Guideline Revising Committee of Japanese Society of Gout and Nucleic Acid Metabolism
Slide19Hyperuricemia
is the cause of
urate
deposition diseases (such as gouty arthritis and renal damage) and is defined as serum urate levels of more than 7.0 mg/dL. The disease affects
people of both genders and all ages
19
Slide20Amongst women, the risk of lifestyle
diseases
increases with rises in serum
urate
levels,
even if serum urate levels are below 7.0 mg/dL. Testing for underlying diseases and lifestyle guidance are carried out, but uric acid lowering
drugs are not indicated.
20
Slide21Treatment of hyperuricemia
What is most important in the treatment
of
hyperuricemia
is the improvement of
lifestyle habits that are related to the development of hyperuricemia and which also easily lead to the development of prognosis related complications such as obesity, hypertension,
and
lipid metabolism abnormalities.
21
Slide22Drug therapy is indicated in cases where
gouty
arthritis occurs repeatedly or gouty
tophus
is diagnosed, and maintenance of serum
urate levels of 6.0mg/dL or lower is desirable.
22
Slide23Drug therapy for asymptomatic
hyperuricemia
is implemented when serum
urate
levels are 8.0 mg/dL or higher as a general indicator, but should be undertaken with caution.
23
Slide24There is scant evidence regarding treatment
for
asymptomatic
hyperuricemia
and consensus
is also insufficient. First of all, patients undergo lifestyle guidance, and then if serum urate levels remain high, drug therapy is considered
24
Slide25In cases of
hyperuricemia
/gout
complicated by
concomitant renal damage or urinary
lithiasis, allopurinol is administered to lower uric acid levels.25
Slide26As renal function declines, it is necessary
to
reduce the allopurinol dosage used
26
Slide27Treatment
of
hyperuricemia
using
allopurinol
is helpful in maintaining renal function in CKD patients. 27
Slide28Losartan
potassium is helpful in
controlling hypertension/
hyperuricemia
in renal transplant patients undergoing cyclosporine therapy.28
Slide29Hyperphosphatemia
treatment with
sevelamer
hydrochloride—used with maintenance
hemodialysis patients—also prevents/reduces hyperuricemia29
Slide30Treatment
of
hyperuricemia
/gout with
concomitant urinary
lithiasisGuidance concerning water intake aims to ensure that patients drink 2,000 mL/day of water or more.
Allopurinol
is the drug of first choice for
the treatment of hyperuricemia complicated
by
concomitant urinary
lithiasis
.
30
Slide31Because
uricosuric
drugs stimulate the
formation
of
urate stones, as a general rule they are not used in the treatment of hyperuricemia cases complicated by concomitant urinary lithiasis.
31
Slide32Using mainly citric acid formulations, the
aim
of urine
alkalinization
is to maintain urine
ph between 6.0 and 7.0. Diet therapy, such as purine intake limitations, also needs to be implemented concurrently.
32
Slide33Allopurinol and urine
alkalinization
drugs
are
effective in preventing the reoccurrence of
calcium oxalate stones associated with hyperuricosuria. 33
Slide34Treatment of hyperuricemia
/gout with
concomitant hypertension
For
hyperuricemia
patients with hypertension complications, first of all lifestyle guidance is carried out with the aim of “avoiding risks to organs overall” by simultaneously improving lifestyle habits related to the
onset
of
hyperuricemia.
34
Slide35Drug therapy prioritizes blood pressure management, and it is desirable to give priority as far as possible to the use of antihypertensive drugs that do not negatively impact uric acid metabolism.
35
Slide36Even when lifestyle guidance and
anti hypertensive
drugs preferable for uric acid
metabolism
are used, commencing
administration of uric acid lowering drugs is considered in cases where serum urate levels are 8.0mg/dL
or higher. It is desirable to
maintain
serum urate levels during treatment to
6.0
mg/
dL
or lower.
36
Slide37Treatment of hyperuricemia
/gout with
concomitant hyperlipidemia
In addition to treating
hyperuricemia
, therapy also aims to treat hyperlipidemia—which is a factor in arteriosclerotic disease—and alleviate the arteriosclerotic disease.
37
Slide38A diagnosis
of hyperlipidemia
is
made when
th
patient has LDL hypercho lesterolemia (LDL cholesterol≧140mg/dL),
HDL
hypocholesterolaemia
(HDLcholesterol
<
40mg/
dL
), or hypertriglyceridemia (
triglycerides≧150mg/
dL
)
38
Slide39Treatment of hyperlipidemia
complicatin
hyperuricemia
/gout
is carried out in accordance with the Arteriosclerotic Disease Prevention Guidelines
39
Slide40Some drugs used to treat hyperlipidemia
also
have an effect on serum
urate
levels, and
so these are considered. In particular, fenofibrate is an effective medicinal agent in cases complicated by hypertriglyceridemia and hyperuricemia, especially hyperuricemia causing a
decreased
uricosuric
effect.
40
Slide41Lifestyle guidance for patients with
hyperuricemia
/gout
Hyperuricemia
and gout are
representative lifestyle diseases. Lifestyle guidance is a non drug therapy aimed at correcting lifestyle
habits
and plays an important role in
treatment regardless of whether or not drug therapy is
implemented.
41
Slide42Lifestyle guidance for
hyperuricemia
/gout
patients
centers on
diet therapy, limitation of alcohol intake, and encouragement of exercise, and reducing obesity is expected to have the effect of lowering serum urate
levels.
42
Slide43In diet therapy, patients are advised about
correct
energy intake, limitations on excessive
purine
and fructose intake, and drinking
sufficient water. Physical activity can be encouraged to improve various pathological conditions of metabolic syndrome.
43
Slide4444
Slide45Exercise daily and reduce weight
Increased
adiposity is associated with higher uric acid levels and an increased future risk of gout, whereas weight loss is associated with lower uric acid levels and a decreased risk of
gout.
Many
patients with gout are overweight or obese, and weight reduction through gradual caloric restriction and exercise can substantially help lower uric acid levels and the risk of gout attacks, in addition to its beneficial effects on associated cardiovascular-metabolic commodities and sequelae.
45
Slide46Limit red meat intake
It
is associated with higher uric acid levels
.
The mechanism behind this increased risk may be multifactorial. The
urate-raising effect of artificial short-term loading of purified purine has been well demonstrated Red meat is the main source of saturated fats, which are positively associated with insulin resistance, which reduces renal excretion of urate.
46
Slide47Tailor seafood intake to the individual
Seafood
intake has been linked to higher serum uric acid levels and increased future risk of gout, which is likely due to its high purine
contents.
Increased
intake of oily fish, other fish, and shellfish was associated with an increased risk of gout. However, given the apparent cardiovascular benefits from fish products. particularly oily fish that are rich in omega-3 fatty acids, it would be difficult to justify a recommendation to avoid all fish intake considering only the risk of gouty flares.
Oily
fish
may be allowed while implementing other lifestyle measures, particularly among gouty patients with cardiovascular comorbidities.
47
Slide48…Tailor seafood intake to the individual
A
mong
patients with gout or
hyperuricemia
, the use of plant-derived omega-3 fatty acids or supplements of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could be considered in the place of fish consumption. Diets enriched in both linolenic acid and EPA significantly suppress urate
crystal induced inflammation in a rat
model
raising an intriguing potential protective role of these fatty acids against gout flares.
48
Slide49Drink skim milk or consume other low-fat dairy products
Up
to two servings daily
.
Low-fat dairy consumption has been inversely associated with serum uric acid levels .Low-fat dairy foods have been linked to a lower incidence of CHD, premenopausal breast cancer, colon cancer, and type 2 diabetes.
49
Slide50Consume vegetable protein, nuts, legumes, and purine-rich vegetables
They
do not increase the risk of
gout
and these food items (especially, nuts and legumes) are excellent sources of protein, fiber, vitamins, and minerals.
Individuals who consumed vegetable protein in the highest quintile of intake actually had a 27% lower risk of gout compared with the lowest quintile.
50
Slide51Nut consumption is associated with several important health benefits including a lower incidence of CHD, sudden cardiac deaths, gallstones, and type 2 diabetes. Legumes or dietary patterns with increased legume consumption have been linked to a lower incidence of coronary heart disease, stroke, certain types of
cancer,and
type 2 diabetes.
The recent healthy eating pyramid recommends 1–3 times daily consumption of nuts and legumes which appears readily applicable among patients with gout or
hyperuricemia
.51
Slide52Reduce alcoholic beverages
52
Slide53Limit sugar-sweetened soft-drinks and beverages
Fructose
contained in these beverages increases serum uric acid levels
.
Fructose
intake has been linked to increased insulin resistance, a positive energy balance, weight gain, obesity, type 2 diabetes, an increased risk of certain cancers,and symptomatic gallstone disease
.
53
Slide54Allow coffee drinking if already drinking coffee
Both
regular and decaffeinated coffee drinking have been associated with lower uric acid levels
Coffee
drinking has been linked to a lower risk of type 2 diabetes, kidney stones,symptomatic gallstone disease, and Parkinson's disease
.
54
Slide55Caffeine tends to promote calcium excretion in urine, and drinking a lot of coffee, about four or more cups per day, may increase the risk of fractures among women.
Caffeine, being a xanthine likely exerts a protective effect against gout similar to allopurinol through xanthine oxidase
inhibition.This
means that intermittent use of coffee or acute introduction of a large amount coffee may trigger gout attacks as allopurinol introduction does.
55
Slide56Consider taking vitamin C supplements
It
has been found to reduce serum uric acid levels in clinical
trials
and has recently been linked to a reduced future risk of gout
. Data suggest that total vitamin C intake of 500 mg/day or more is associated with a reduced risk.Potential cardiovascular benefit of vitamin
C
may also be relevant among gout patients, because of their increased risk of cardiovascular morbidity and mortality
.
Given
the general safety profile associated with vitamin C intake, particularly within the generally consumed ranges (e.g. tolerable upper intake level of vitamin C <2000 mg in
adults),
vitamin C may provide a useful option in the prevention of gout.
56
Slide57Vitamin C
Vitamin C is an essential water-soluble antioxidant vitamin in humans, which has been shown in laboratory tests to exert a uric acid-lowering effect by inhibiting the enzyme xanthine oxidase
.
57
Slide58Cherries
Cherries are a traditional gout treatment rich in polyphenol antioxidants
,and
a small set of clinical cases in the 1950's documented decreased duration and severity of gout attacks in three people on cherry-supplemented diets
.
Two more recent investigations have demonstrated a potential role of cherries in the management of gout, although they present conflicting mechanisms for this action. After a single dose of 280 g cherries, the blood urate levels in 10 healthy women dropped by 14% after 5 hrs, while urinary urate levels increased
.
58
Slide59Fiber
An analysis of fiber intake data in 9,384 adults without cancer, diabetes or heart disease from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 revealed a significant association between higher fiber intake and lower
hyperuricemia
risk.
While these mechanisms for this reduction is unknown, dietary fiber may inhibit purine or adenine absorption in the digestive system
.Fiber has also been shown to reduce other independent risk factors for gout, including hypertension and high cholesterol
59
Slide60Folate
A small case-controlled study of 92 gout patients and 92 gout-free controls demonstrated a statistically significant reduction in the risk of gout amongst persons who consumed over 51.5 mcg/day of folate from food sources
No
significant effects on gout risk were observed for vitamins A, E, or the other B vitamins in this study.
60
Slide61Chinese Herbs
Several Chinese medicinal plants have been tested for xanthine oxidase inhibitory activity.
The
most active was the methanol extract of Chinese cinnamon (
Cinnamomum
cassia), followed by Chrysanthemum indicum and Lycopus europaeus. Among water extracts, the strongest inhibition was observed with Polygonum
cuspidatum
, which is an excellent source of the polyphenol
resveratrol .
61
Slide62Flavonoids
Flavonoids may lower blood uric acid through their ability to inhibit the enzyme xanthine
oxaidase
; olive leaf constituents,
have
all shown this ability in laboratory experiments.62
Slide63Drugs
Slide64urate
-lowering therapy (ULT) should be considered in patients with 1 or more tophi, ≥2 attacks per year, chronic kidney disease (CKD; stage 2 or worse), or a history of
urolithiasis
.
64
Slide65initiating ULT with either
allopurinol;
probenecid
is recommended as an alternative first-line agent when either allopurinol
is
contraindicated, or when a patient has demonstrated intolerance toallopurinol. ULT can be started during an acute gout attack; the serum urate level should be monitored every 2-5 weeks during ULT titration and every 6 months after the target serum level (<6 mg/dL) has been reached.
65
Slide66Allopurinol Dosing
Starting
allopurinol dose should not exceed 100 mg/day, and patients with CKD of stage 4 or higher should be started at 50 mg/day. Dosages should be titrated up every 2-5 weeks to achieve target serum uric acid and can go above 300 mg/day as long as the patient is educated and monitored for adverse events.
66
Slide67Uricosuric Therapy
When using a
uricosuric
as ULT monotherapy, the ACR TFP recommends
probenecid
. First-line use of probenecid is contraindicated in patients with a history of urolithiasis
67
Slide68Thank you
Caption
68