Hyperuricemia is defined as a serum urate concentration above 6.8 mg/dL. It can be caused by either underexcretion of uric acid by the kidneys in over 90% of cases or overproduction in under 10% of cases. The prevalence of hyperuricemia and gout is increasing due to aging populations, obesity, metabolic syndrome, and dietary factors like alcohol and fructose consumption. Left untreated, hyperuricemia may progress to chronic gout or urate nephropathy. Testing involves measuring serum uric acid levels as well as kidney function to determine the cause and monitor treatment effectiveness.

1. Hyperuricemia
Safwat EL-Araby
Rheumatology
Al-Azhar / EGYPT
Prevalence
Pathophysiology
Types
Triggers & causes
Outcome
Testing & Work up
Definition

2. Definition

3. Level of Saturation
Sugar Crystals
Salt Crystals
Cholesterol Crystals
Sugar Crystals

4. Physically : Serum Urate Level of Saturation
6.8 mg/dL.
Level of Saturation
Hyperuricemia :
is defined as a serum urate concentration 6.8 mg/dl
404 mcmol/L
0.40 mmol/L
Hyperuricemia +
Saturation +
Nucleation +
Crystallization +
Deposition =
Acute attack of gout &/or Crystal growth

5. Prevalence

6. 30 %
10 %
Top Causes of Joint Pain
Gout = 1/10
Regional Pain Syndromes were excluded

7. Prevalence of
Hyperuricemia =
Gout
( Classic )( Even Normouricemic ) +
Asymptomatic Hyperuricemia +
Intercritical Hyperuricemia +
MSU deposition diseases
( Non classical/Unusual presentations )
( Silent deposition )
Hyperuricemic patients may include :

8. Effect of Environment & Life Style

9. USA
EU
Japan
How many patients have Hyperuricemia ?
How many developed Gout ?
How many diagnosed ?
How many receiving ULT ?
1/3
1/2
2/3
> 330 > 508 > 127
6.5% 4% 7.5%
Industrial ( Developed ) World

10. Prevalence :
Hyperuricemia : 2.6 % to 47.2 % in various population groups
Gout incidence : 1 % to 15 % increases with serum urate level
Clear increase in incidence in recent years, Why ?
Rising incidence and prevalence of Gout and Hyperuricemia
attributed to the
Aging population
Health Epidemics :
Increased in Rich Industrial Western Societies ( Overindulgence )
Also in less industrial countries because of increased Longevity , Dietary habits , Obesity & Metabolic syndrome
.
Obesity,
Metabolic syndromes,
Type 2 Diabetes,
Hypertension ,
Thiazide Diuretics ,
CKD
Dietary issues with
regards to Purine and Fat
intake

11. Associations / Triggers / Risk factors / Causes for secondary / Strategy for Therapy
Those patients more susceptible to develop Hyperuricemia & gout

12. Incidence of Gout is Higher amongst those with Higher UA concentrations
Only 1/3
developed Gout
Who ?
Those

13. > 60 % of gouty patients have Metabolic Syndrome
Each element of MS are 2-3 times more frequent amongst gouty patients

15. Above age of 40 : 70% of patients with MS , are Gouty

16. Pathophysiology

17. Dietary Nucleic acids ( DNA & RNA )
Degraded in the small intestine lumen
Cellular Nucleic acids ( DNA & RNA )
DNA/RNA in cells degraded (Turnover)
Purine Turnover
Sources of Uric Acid
Fasting

18. High Fructose Corn Syrup
is a low-cost sweetener that replaced sugar in thousands of products over the past 30 years.
In 1970,
Americans consumed less than
a pound of the syrup per year.
In 2005,
the average was
42 pounds, according to The
Seattle Times.

19. Purine Turnover
Sources of Uric Acid
~10% of filtered
Uric acid is excreted
Overproduction is associated with Overexcretion / Donot use uricosurics
Excretion
Locations of Urate Deposition = Locations of high acidity / filtration / reabsorption /
Secretion OR Excretion

20. How to differentiate ?
> 90%

21. End result of both : is increased Serum urate concentration above level of Saturation

22. Types
According to Pathophysiology
According to Causative Factors
According to Triggers
According to Severity
According to the Course
According to associations
According to Co-morbidities
Collecting good data = Optimal Strategy

23. It is caused by decreased Renal UA excretion in > 90% of patients
and Overproduction of urate in < 10% of patients.
No Renal disease
No Congenital disease
No Myeloproliferative disease
According to known Causative Factors
Primary Hyperuricemia
Some but not all cases of primary gout have a Genetic Basis.
Unknown

24. It is related to Overproduction OR Decreased Clearance as a direct or indirect consequence of the primary disease process.
What are the primary disorders causing :
Urate Overproduction & Those causing
Urate Underexcretion
There is primary congenital or acquired disease
Secondary Hyperuricemia
Known Cause
According to known Causative Factors

25. Causes
2ry Hyperuricemia

26. Secondary Hyperuricemia
Cause Increased Urate production Decreased Urate Excretion

27. Diuretic-induced volume depletion
Two Mechanisms : decreased filtered load and
enhanced tubular reabsorption of urate.
Drug-Induced
Hyperuricemia :
Diuretic therapy
Currently represents one of the most important causes of 2ry Hyperuricemia
Diuretics : Enhance diuresis – Enhance UA excretion / decreased volume / increased concentration / decreased reabsorption & increased secretion /
reducing hyperuricemia
Regarding hyperuricemia : difference between diuresis of Diuretics & Hydration

28. Drug-Induced Hyperuricemia :
Other drugs lead to Hyperuricemia by a Renal mechanism : Includes :
Low-dose Aspirin,
Pyrazinamide,
Nicotinic acid,
Ethambutol,
Ethanol,
Cyclosporine.
Are they : Causes / Risk Factors / Triggers
Antiplatelets
Anti-tuberculous
Niacin for blood fat
Anti-tuberculous : Children
Ethanol,
RA
Nicotinic acid (also known as niacin) is vitamin B3, which occurs naturally in food. Used as a medicine, it can improve levels of blood fats (lipids)
such as cholesterol and triglycerides. Nicotinic acid works by reducing the amount of 'bad' cholesterol and triglycerides made by the liver.

29. The consumption of some foods, might be protective , especially :
Environmental Factors :
Certain foods promote Hyperuricemia and Gout, including :
Beer, which is rich in purine, carries the Highest Risk
Consumption of :
Sweeteners containing Fructose also contribute to Hyperuricemia.
Alcohol
Seafood
Red meat
Milk
Yogurt,
is not associated with an increased risk of gout.
Oatmeal and
Purine Rich Vegetables
(e.g., Peas, Mushrooms, Lentils,
Spinach, and Cauliflower)

30. What are the diseases should be treated before ULT ?
What are the medications should be optimized before ULT ?
What are the foods should be reduced before ULT ?
What are the foods should be restricted OR avoided ?
What are foods should be encouraged ?
What is the disease that causing
overproduction & underexcretion of urates ?
What is wonderful :
Eltroxin may help ULT ?
Vitamin-D analogue may help
Uricosurics for psoriasis but not Sarcoidosis
Hyperuricemia may be fatal for pregnant with Toxemia
To avoid low dose of aspirin : 350 mg weekly
Dehydration causing Hyperuricemia &
Fasting triggering acute attack of Gout ?

31. Hyperuricemiawith Acute
Gouty Attack
Refractory Hyperuricemia
Hyperuricemia :
Urate Nephropathy
Hyperuricemia
with chronic Tophaceous gout
Hyperuricemia
More frequent / Severe / Duration & Polyarticular
Classification of Hyperuricemia :
in relation to Course
Why ?
2ry Hyperuricemia / Diuretic + low dose aspirin

32. Why ?

34. According to Severity Serum Urate Concentrations
Why some patients develop Gout once they achieve point of saturation ?
Hyperuricemia / Incidence of gout
Hyperuricemia / cumulative incidence of First
Attack
Hyperuricemia / Pain Severity
> 9mg/dl
< 7mg/dl
2ry Hyperuricemia / Diuretic + low dose aspirin / intercritical

35. Asymptomatic H
Asymptomatic with deposition
During acute Gouty attack
Intercritical
Silent Tophi
Chronic Tophaceous gout
Secondary
Primary
Types of Hyperuricemia
Urate Level
Age
Associations
Refractory
Urate Nephropathy
Is strategy of therapy , the same ?
Dialysis / with & without anuria
Transplanted
Kidney Functions / eGFR

36. Asymptomatic H
Asymptomatic with deposition
During acute Gouty attack
Intercritical
Silent Tophi
Chronic Tophaceous gout
Secondary
Primary
Types of Hyperuricemia
Urate Level
Transplanted
Associations
Refractory
Urate Nephropathy
Is strategy of therapy , the same ?
Age
Dialysis with & without Anuria
K Functions/eGFR

37. Course without Therapy

38. Hyperuricemia
Underexcretion Overproduction
Asymptomatic
Intercritical
Tophaceous
No underlying disease
Underlying disorder
According to the course
1ry & 2ry
90%
1ry & 2ry
10%
No underlying disease
Underlying disorder
According to severity
Fate of Hyperuricemia
Outcome
Neglected cases

39. Hyperuricemia
Underexcretion
Overproduction
Dialysis
with & without Anuria
Drug-induced
Tophaceous Gout
With Acute attack
Intercritical
Asymptomatic
< 8 mg/dl / < 9 / < 11 / >11 / > 13
Kidney Functions : GFR
Is treatment,the same for all these situations ?
Transplanted
Is strategy of therapy of secondary hyperuricemia due to over production or under excretion is
different
For treatment of hyperricemia with underexcretion
Is there any difference between 1ry & 2ry

40. Hyperuricemia ( 10.5 mg / dl ) /
66 years old /
Diuretic + Low dose Aspirin /
Intercritical /
eGFR ( 60 ) /
165/90 mmHg /
Dyslipidemic
( To be more specific Hypertriglycerdemia )
Write prescription for following patient
Write prescription for hyperuricemic patient with SUA ( 10.6 mg/dl )

41. Outcome

42. A period of Asymptomatic Hyperuricemia lasts up to
20 years
or more before the
The First Gout attack generally occurs at :
age 40 to 60 years in men and after
age 60 years in women.
Age of 20 years of Hyperuricemia
Age of Low Dose of Aspirin
Age of Diuretics
Menopause & after
Initial attack of Gout OR
Nephrolithiasis.

43. Asymptomatic
But
,
may

45. Gout
Chronic
Tophaceous Gout
Systemic
Features
Non classic
Unusual
presentation

46. Testing

47. Testing : For Hyperuricemia
Serum Uric Acid Level 6.8 mg / dl
404 mcmol / L
0.40 mmol / L
Kidney Function Tests :
Total UA excretion / 24 hours
Creatinine Clearance
Urinary UA to Creatinine Ratio
Microalbuminuria
Urates in Sediment
pH
Full Urine Analysis
Serum Creatinine
eGFR
Creatinine Clearance
BUN

48. Serum Uric Acid Level :
It is of limited usefulness during acute attack
Serum Uric Acid Level :
It may be normal during acute gout attack
Serum Uric Acid > 6.8 mg/dl ( 404 mcmol/L )
sufficient to precipitate crystals ,
although some laboratories may list higher upper limits of normal
Serum Uric Acid Levels :
They are helpful in monitoring effects of Antihyperuricemic therapy
Leukocytosis
May occur in acute gout

49. Associations

50. Associated Conditions :
Obesity
Hypertriglyceridemia
Glucose intolerance
Hypertension
Atherosclerosis, and
Coronary Artery Disease
Hypothyroidism.
If you have Hyperuricemia OR Gout : Think about :
Work up for detection :

51. Testing : For Associations
Lipid Profile Dyslipidemia
High Triglycerides
Low HDL-Cholesterol
Insulin Resistance
Visceral Obesity
BMI
Blood Sugar Fasting
Random
Hba1c
Measure Blood Pressure

52. Testing : For Causes
CBC Myeloproliferative disorders :
Polycythemia
Lymphoproliferative disorders
T3 , T4 , TSH
Hypothyroidism
Hyperparathyroidism
PTH

53. When Facing Hyperuricemia ?
Severity ( SUA )
Kidney Function Tests
Look for : Associations
Look for Causes
MsK US : For detection of Urate deposition in possible locations
If asymptomatic Hyperuricemia
I will ask myself : Why only 1/3 of patients develop Gout ?
What instructions to avoid progression to Gout ?
e.g. High SUA OR associations