• Credits
  - Section Writer: Dr. Om J Lakhani
  - Section Editor: Dr. Om J Lakhani

• Source: Valsaraj R, Singh AK, Gangopadhyay KK, Ghoshdastidar B, Goyal G, Batin M, Mukherjee D, Sengupta U, Chatterjee S, Sengupta N. Management of asymptomatic hyperuricemia: Integrated Diabetes & Endocrine Academy (IDEA) consensus statement. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020 Mar 1;14(2):93-100.

• Q. What is the upper limit of uric acid levels in men and women?

  • Asymptomatic Hyperuricemia is defined as
  • Uric acid More than 7 mg/dl in men
  • Uric acid More than 6 mg/dl in women

• Q. What should be the physiological definition of Asymptomatic Hyperuricemia?

  • The physiological definition should be Uric acid >6.8 mg/dl
  • This is because the 37 degrees centigrade, and pH of 7.0, the uric acid tends to get deposited in the peripheral joints.

• Q. What is the currently available method used for the diagnosis of Asymptomatic Hyperuricemia?

  • Uricase method

• Q. What precautions must be taken before taking a sample for uric acid?

  • Must be done after an overnight fast
  • Avoid alcohol intake the day before
  • Avoid vigorous exercise before collecting a sample
  • Avoid drugs that can potentially interfere with uric acid levels
  • Avoid dehydration
  • Avoid smoking (this reduces uric acid levels)

• Q. What are the clinical consequences of Asymptomatic Hyperuricemia?

  • 1. Gout
  • 2. Renal calculi
  • 3. CKD - development, and progression
  • 4. Metabolic syndrome and insulin resistance
  • 5. Cardiovascular disease
  • 6. Acute urate nephropathy

• Q. Who should be screened for Asymptomatic Hyperuricemia?

  • 1. Patients with gout
  • 2. Patients having renal calculi
  • 3. Patients with CKD (Stages 3-4)
  • 4. Patients on drugs known to produce Asymptomatic Hyperuricemia
  • 5. Patients receiving cancer chemotherapy
  • 6. Patients with metabolic syndrome
  • 7. Patients with cardiovascular disease

• Q. Which are the drugs known to produce Asymptomatic Hyperuricemia?

  • 1. Diuretics - loop and thiazide
  • 2. Testosterone
  • 3. Low dose Aspirin (<325 mg)
    • Low dose aspirin- produces hyperuricemia
    • High dose aspirin -reduces hyperuricemia
  • 4. Cancer chemotherapy
  • 5. Nicotinic acid
  • 6. Anti-tubercular drugs
  • 7. Levodopa
  • 8. Immunosuppressants- Tacrolimus and Cyclosporine

• Q. How do diuretics produces Asymptomatic Hyperuricemia?

  • 1. By increasing urate reabsorption from proximal tubule
  • 2. Creating a situation of mild fluid depletion that increase urate reabsorption

• Q. Is Asymptomatic Hyperuricemia associated with thyroid dysfunction?

  • A study by Giordano et al. showed that hyperuricemia is associated with both hyperthyroidism as well as hypothyroidism ^[1]
  • In hyperthyroidism is due to increased urate production
  • While in hypothyroidism, it is due to reduced urate clearance
  • Hyperparathyroidism also has a link with Asymptomatic Hyperuricemia

• Q. Is there a link between Asymptomatic Hyperuricemia and cardiovascular disease?

  • Several epidemiological studies have shown a link between Asymptomatic Hyperuricemia and increased risk of cardiovascular disease and increased mortality
  • Blood pressure especially tends to have close relation with hyperuricemia
  • It is also a risk factor for increased mortality in heart failure

• Q. Is Asymptomatic Hyperuricemia is a cause or effect?

  • It is unclear
  • It seems it is neither a cause nor an effect but simply a marker of metabolic syndrome
  • It is also a marker of reduced tissue perfusion
  • There is a direct correlation between Asymptomatic Hyperuricemia and Insulin resistance

• Q. Is Routine testing for serum uric acid level in a completely asymptomatic patient as a prognostic tool or screening of cardiometabolic risk appropriate or not?

  • Since we have better tools available for cardiovascular risk screening and since treatment or correction of asymptomatic hyperuricemia has not been proven to reduce cardiovascular risk in clinical trials, routine screening for hyperuricemia in patients with cardiovascular disease is NOT indicated.

• Q. What are the metabolic abnormalities that need consideration in a patient with Asymptomatic Hyperuricemia, assuming that uric acid levels can have prognostic significance for that associated comorbidities?

  • Asymptomatic Hyperuricemia is a part of the broad universe of Insulin resistance syndrome, which also includes
    • Central adiposity
    • High triglycerides
    • Low HDL
    • Hypertension
    • Pre-diabetes
    • Fatty liver

• Q. Which carbohydrate has been linked with Asymptomatic Hyperuricemia?

  • Fructose

• Q. What is the relation between uric acid and reactive oxygen species?

  • Uric acid is a natural antioxidant
  • it scavenges oxygen radicals and protects the erythrocyte membrane from lipid oxidation

• Q. Does uric acid-lowering therapy have any benefit in the prevention of progression of CKD?

  • Yes
  • The benefit is limited to CKD stage 3 or 4
  • febuxostat is preferred in such cases

• Q. Should uric acid-lowering therapy be used for patients with high cardiovascular risk to reduce the risk of cardiovascular disease?

  • No
  • No RCT has shown any benefit of the same
  • However, reduction of uric acid has been shown to reduce the blood pressure

• Q. Broadly, what types of food are likely to be associated with Asymptomatic Hyperuricemia?

  • Foods rich in Purine are likely to be associated with increased uric acid
  • Dietary restrictions should be recommended to all patients with Asymptomatic Hyperuricemia irrespective of symptom status
  • Animal sources rich in purine must be avoided
    • Red meat
    • Organ meat
    • Seafood protein (Fish and shellfish)
  • Plant sources rich in purine are not associated with gout and need not be avoided
    • Peas
    • Lentils
    • Beans
    • Spinach
    • Mushroom
    • Asparagus
  • Alcohol intake- restrict
    • Beer especially is most likely to be associated with Asymptomatic Hyperuricemia
    • Red wine may be protective to some extent

• Q. Intake of what food product reduces the risk of Asymptomatic Hyperuricemia?

  • Low-fat milk and milk products reduce uric acid levels and are recommended
  • Cherries and Vitamin C- also reduce uric acid
  • Coffee is also found to have a beneficial effect

• Q. What are the dreaded complications of allopurinol?

  • Steven Johnson syndrome
  • DRESS syndrome
  • Leukopenia

• Q. Give a broad outline for management of asymptomatic Asymptomatic Hyperuricemia as suggested by Indian guidelines

-ULT = Urate lowering therapy

• Q. Which drug should be used for urate-lowering if treatment is indicated?

• Q. What should be the target of the uric acid levels in cases where treatment with Urate lowering therapy is indicated?

  • It should be between 3-6 mg/dl
  • Levels <3 mg/dl can lead to neurodegenerative disorders

• Q. What is the role of HLA testing before starting allopurinol?

  • Ideally, patients should be tested for HLA-B*5801 before starting allopurinol
  • This is because patients with HLA-B*5801 are at higher risk of developing severe cutaneous reactions secondary to allopurinol which is SJS/DRESS
  • This test is available with Lal path lab

• Q. Which drugs used in the cardiometabolic space have urate-lowering properties?

  • ARB (esp Losartan)
  • CCB
  • Statin
  • Fenofibrate
  • Metformin
  • SGLT2i
  • Orlistat
  • High dose aspirin

• Q. Is there any data to suggest a reduction of uric acid with the use of SGLT2i?

  • Yes
  • This has been proven in a meta-analysis by Yakai Xin et al ^[2]
  • It has also been shown to reduce the risk of gout

• Q. How does SGLT2i lead to a reduction in uric acid levels?

  • Glucose is reabsorbed by PCT via SGLT2 and GLUT9
  • Uric acid is absorbed via URAT1 and GLUT9
  • So, by inhibiting the absorption of glucose via SGLT2, there is competition over the use of the GLUT9 channel between glucose and uric acid
  • Hence this leads to reduce uric acid reabsorption
  • Source : Bailey et al ^[3]
  • 

• Q. Does Asymptomatic Hyperuricemia have an impact on Diabetes Mellitus and Its Chronic Complications- microangiopathy and macrovascular disease?

  • This is an area of controversy
  • Though pathophysiological, it is plausible that hyperuricemia may have worsened the diabetes-related microvascular and macrovascular complications mainly via endothelial dysfunction; there is also a school of thought that it is primarily a marker and not a cause

YouTube video on a panel discussion on "Asymptomatic Hyperuricemia"