Hyperuricemia/gout diagnosis and treatment pathway

1. Diagnosis of Hyperuricemia:

1: Fasting blood uric acid levels greater than 420umol/L on two different days. Adults, male or female.

2: Classification: It is recommended that young patients with gout or those with a family history be diagnosed based on 24-hour uric acid excretion (UUE) and renal fractional uric acid excretion (FEUA):

(1) Renal poor excretion type: 24-hour uric acid excretion (UUE) is less than or equal to 600 mg.d-1.(1.73 m2)-1 and renal uric acid excretion fraction (FEUA) is less than 5.5%.

(2) Renal overload type: 24-hour uric acid excretion (UUE) is greater than 600 mg.d-1.(1.73 m2)-1 and renal uric acid fraction excretion (FEUA) is greater than or equal to 5.5%.

(3) Mixed type: 24-hour urine uric acid excretion is greater than (UUE) 600 mg.-1.(1.73m2)-1. and renal uric acid excretion fraction (FEUA) is less than 5.5%.

(4) Other types: 24-hour urine uric acid excretion is less than or equal to (UUE) 600 mg.-1.(1.73m2)-1. and renal uric acid excretion fraction (FEUA) is greater than or equal to 5.5%.

3: It is recommended that under the low-purine diet, the 24-hour urine uric acid excretion and renal uric acid excretion fraction are two indicators for more accurate classification.

Gout Diagnosis:

2015 American College of Rheumatology (ACR)/European Union Association for Rheumatology (EULAR) classification criteria for gout

1Subclinical gout:

In patients with asymptomatic hyperuricemia, joint ultrasound, dual-energy CT, or X-ray may reveal urate crystal deposition or tophi erosion.

2. Refractory gout:

Refers to one of the following three conditions:

(1) After adequate use of conventional uric acid-lowering drugs alone or in combination for a sufficient course of treatment, serum uric acid remains greater than or equal to 360 μmol/L.

(2) Gout attacks still occur more than or equal to 2 times per year despite receiving standardized treatment.

(3) The presence of multiple or progressive tophi.

3 New gout classification criteria:

(1) Necessary conditions: At least one occurrence of joint swelling, pain or tenderness.

(2) Sufficient condition: urate crystals or tophi are found in joints or synovial fluid.

(3) If this sufficient condition is not met, gout can be diagnosed based on the cumulative score of clinical symptoms, signs, laboratory and imaging examination results, which is greater than or equal to 8 points.

Healthy lifestyle for patients with hyperuricemia, hyperuricemia and gout;

(1) Control your weight and exercise regularly.

(2) Limit the intake of alcohol and high-purine and high-fructose foods.

(3) Encourage the intake of dairy products and fresh vegetables and drink enough water.

(4) The intake of soy products (tofu) is not recommended or encouraged.

(5) Gout is a lifestyle-related disease, closely related to long-term high-calorie diet and high alcohol intake.

4. Factors affecting patients with hyperuricemia and gout;

(1) Always keep the blood uric acid level within the ideal range of 240-420umol/L.

(2) The fundamental cause of the occurrence and development of hyperuricemia, gout and related complications is the increase in blood uric acid levels.

(3) Long-term standard of serum uric acid:

A can reduce the frequency of gout attacks,

BPreventing the formation of tophi

C prevents bone destruction,

D Reduce mortality,

Improve the quality of life of patients,

F is the key to preventing gout and its related complications.

(4) Long-term or even lifelong use of uric acid-lowering drugs may be required.

Five possible dangers of hyperuricemia and gout:

(1) Regularly screen and monitor target organ damage and control related complications.

(2) It is a chronic, systemic disease that can cause damage to multiple target organs and affect life expectancy.

(3) There is a clear causal relationship between kidney stones and chronic kidney disease.

(4) Elevated blood uric acid is an independent risk factor for cardiovascular disease, diabetes and other diseases.

(5) For patients with asymptomatic hyperuricemia and renal damage, uric acid-lowering therapy can significantly improve their renal function and delay the progression of chronic renal insufficiency.

(6) Significantly reduce systolic and diastolic blood pressure levels in hypertensive patients.

6. Treatment timing and control goals for asymptomatic hyperuricemia:

When to treat:

(1) Serum uric acid level is greater than or equal to 540umol/L.

(2) The serum uric acid level is greater than or equal to 480 μmol/L and there is one of the complications, such as hypertension, diabetes, coronary heart disease, lipid metabolism disorder, obesity, stroke, heart failure, uric acid nephrolithiasis, renal impairment (stage 2 renal insufficiency)

Control objectives:

(1) For patients without complications, serum uric acid should be controlled at less than 420umol/L. Range: 540-420umol/L

(2) For patients with complications, the blood uric acid level should be controlled within the range of 480-360umol/L

Seven gout treatment opportunities and control goals:

When to treat:

(1) Serum uric acid greater than or equal to 480umol/L

(2) Serum uric acid level greater than or equal to 420 umol/L and one of the following complications: gout attacks greater than or equal to 2 times/year, tophi, chronic gouty arthritis, kidney stones, chronic kidney disease, hypertension, diabetes, dyslipidemia, stroke, ischemic cardiomyopathy, heart failure and age of onset less than 40 years.

(3) Start uric acid-lowering drug treatment 2-4 weeks after the acute gout attack is completely relieved.

(4) For patients with acute gout who are taking uric acid-lowering drugs, it is not recommended to stop taking these drugs.

Control objectives:

(1) Gout patients should control their blood uric acid level to less than 360umol/L

(2) Complications: control blood uric acid level to less than 300umol/L

(3) It is not recommended to keep blood uric acid below 180umol/L for a long time

8. Uric acid-lowering drug selection for patients with hyperuricemia and gout:

Consider drug indications, contraindications, and classification of hyperuricemia:

(1) First-line drugs for gout: allopurinol, febuxostat, benzbromarone

(2) First-line drugs for asymptomatic hyperuricemia: allopurinol or benzbromarone

(3) If the serum uric acid level does not reach the target after sufficient dose and duration of treatment, two uric acid-lowering drugs with different mechanisms can be used in combination.

(4) The combined use of uricase and other uric acid-lowering drugs is not recommended.

The principle of allopurinol:

(1) The liver metabolizes it into active hydroxypurinol, which is then excreted from the body through the kidneys.

(2) It is easy to accumulate in the body when renal function is impaired, increasing the risk of drug poisoning.

(3) Renal insufficiency stage 1-2 with glomerular filtration rate greater than or equal to 60 ml.min. The starting dose of allopurinol is 100 mg/d. Increase by 100 mg/d every 2-4 weeks, with a maximum dose of 800 mg/d.

(4) For patients with stage 3-4 renal insufficiency and glomerular filtration rate of 15-59 ml.min, the initial dose of allopurinol is 50 mg/d, which is increased by 50 mg/d every 4 weeks to a maximum dose of 200 mg/d.

(5) It is contraindicated for patients with stage 5 renal impairment with a glomerular filtration rate less than 15 ml/min.

Principle and usage of decabenzbromarone:

(1) Inhibit renal proximal tubular uric acid transporter 1, inhibit renal tubular uric acid reabsorption, and promote uric acid excretion.

(2) Suitable for patients with hyperuricemia and gout with reduced renal uric acid excretion.

(3) It is not recommended for patients with excessive uric acid synthesis or high risk of kidney stones.

(4) When taking benzbromarone, you should drink plenty of water and alkalize your urine.

(5) It is the first-line medication for hyperuricemia and gout.

(6) The initial dose is 25 mg/day. If the blood uric acid level still does not reach the target after 2-4 weeks, the dose can be increased by 25 mg/day, with a maximum dose of 100 mg/day.

(7) Liver function should be closely monitored during use. Benzbromarone should be used with caution in patients with combined liver function.

(8) For those who still fail to reach the target, two uric acid-lowering drugs with different mechanisms can be used in combination.

11. Febuxostat medication principle and usage:

(1) Specific xanthine oxidase inhibitors.

(2) Especially suitable for patients with chronic renal insufficiency.

(3) Due to its high price and potential cardiovascular risks, European and American guidelines recommend febuxostat as an alternative to allopurinol. It is used when allopurinol is intolerant or ineffective.

(4) The expert group recommends febuxostat as the first-line drug.

(5) The initial dose is 20 mg/day. If the blood uric acid level does not reach the standard after 2-4 weeks, the dose can be increased by 20 mg/day. The maximum dose is 80 mg/day.

(6) Elderly people with cardiovascular diseases should use the drug with caution and pay close attention to cardiovascular events.

12. Urine pH:

(1) Low pH less than 6 is an important cause of uric acid kidney stones.

(2) Benzbromarone can cause a significant increase in uric acid concentration in urine, increasing the formation of uric acid kidney stones.

(3) The morning urine pH is less than 6. Patients who use uric acid excretion-promoting drugs should monitor the morning urine pH regularly.

(4) Patients with kidney stones should maintain the pH of urine between 6.1 and 7.0.

(5) Although urine pH greater than 7.0 increases the dissolution of uric acid, it also increases the incidence of calcium salt stones.

(6) The recommended optimal morning urine pH for patients with hyperuricemia and gout is 6.2-6.9.

(7) Drugs for alkalinizing urine: citric acid preparations, sodium bicarbonate tablets.

13. Anti-inflammatory and analgesic treatment for acute gout attack:

(1) Low-dose colchicine or NSAID (sufficient dose, short course of treatment).

(2) For patients with intolerance, poor efficacy or contraindications, systemic glucocorticoids are recommended.

(3) For patients at risk of gastrointestinal bleeding or those taking low-dose aspirin for a long time, selective oxidase-2 inhibitors should be considered.

(4) For patients with acute gout attacks involving multiple joints, large joints, or combined with systemic symptoms, systemic glucocorticoids should be considered.

(5) For patients with a pain visual acupuncture score of 7 or more, or with arthritis in more than 2 large joints or multiple joints, or with poor response to one medication, it is recommended to use two anti-inflammatory analgesics in combination: low-dose colchicine + NSAID. Or low-dose colchicine + systemic glucocorticoids.

Tetradecanoic Urine:

(1) The main methods for preventing and dissolving uric acid kidney stones.

(2) Commonly used drugs are sodium bicarbonate and citric acid preparations.

1. Sodium bicarbonate

(1) Suitable for patients with chronic renal insufficiency and metabolic acidosis. Dosage: 0.5-1.0g/3 times/d.

(2) The main adverse reactions are flatulence and gastrointestinal discomfort. Long-term use should be cautious of increased blood sodium and hypertension.

(3) If the bicarbonate concentration in the blood is greater than 26mmol/L, the risk of heart failure will increase. If the bicarbonate concentration in the blood is less than 22mmol/L, the risk of kidney disease will increase. The bicarbonate concentration in the blood should be maintained at 22-26mmol/L.

2Citrate preparations

(1) Mainly used for patients with uric acid kidney stones, cystine stones and hypocitraturia.

(2) The dosage is mainly determined by the urine pH value. The general dosage is 9-10g/d, and the course of treatment is 2-3 months.

(3) Liver function and electrolytes must be maintained during the first use.

(4) When potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, antihypertensive drugs, and NSAIDs are used together, they can easily cause hyperkalemia and should be carefully monitored.

(5) It is contraindicated for patients with acute or chronic renal failure, severe acid-base imbalance, chronic urinary tract urea decomposition infection, or those who are absolutely contraindicated for the use of sodium chloride.

Fifteen principles of NSAID use:

(1) NSAIDs are the first-line medication for acute gout attacks and should be taken in sufficient doses in the early stages.

(2) Drugs with rapid onset of action and few gastrointestinal reactions are preferred.

(3) Use with caution in the elderly, patients with renal insufficiency, or patients with a history of gastrointestinal bleeding, ulcers, or perforation.

(4) The first choice is the selective oxidase inhibitor (COX-2) etoricoxib, which has little gastrointestinal reaction.

(5) Non-selective NSAIDs can affect the anticoagulant activity of low-dose aspirin and increase upper gastrointestinal adverse reactions. For gout patients who take low-dose aspirin for a long time, celecoxib is recommended as a first choice.

(6) All NSAIDs can cause renal ischemia, inducing and aggravating acute and chronic renal failure.

(7) NSAIDs should be used with caution or prohibited in patients with gout and renal insufficiency. Long-term use is not recommended for patients with a glomerular filtration rate of less than 60 ml/min. NSAIDs should not be used for patients with a glomerular filtration rate of less than 30 ml/min.

Principles of colchicine use:

(1) First-line medication for acute gout attacks.

(2) Low-dose colchicine is also effective in treating acute gout attacks, and the adverse reactions are significantly reduced.

(3) The initial dose of colchicine is 1 mg, then 0.5 mg is added after 1 hour, and then changed to 0.5 mg qd or bid after 12 hours.

17. Measures to prevent gout attacks in patients with gout during the initial stage of uric acid-lowering drug treatment:

(1) Small doses of colchicine 0.5mg-1mg/d can prevent gout attacks.

(2) Maintain for at least 3-6 months.

(3) For patients with renal insufficiency, the dosage should be adjusted according to the glomerular filtration rate.

(4) For patients who cannot tolerate colchicine, low-dose NSAIDs (no more than 50% of the regular dose) or glucocorticoids (prednisone ≤ 10 mg/d to prevent attacks) are recommended for at least 3-6 months.

(5) It is recommended to take small doses of uric acid-lowering drugs and increase the dose slowly to avoid or reduce gout attacks.

18. Principles of glucocorticoid use during acute gout attacks:

(1) European and American guidelines recommend it as a first-line anti-inflammatory analgesic drug.

(2) The expert group listed it as a second-line analgesic drug because it is necessary to prevent the abuse of hormones and repeated use to increase the incidence of tophi.

(3) Systemic glucocorticoids are only recommended when acute gout attacks involve multiple joints, large joints, or are combined with systemic symptoms.

(4) Oral prednisone 0.5 mg.kg/d, then discontinue medication after 3-5 days. Other hormones: Dexamethasone/betamethasone should be exchanged according to equivalent anti-inflammatory doses.

(5) When gout attacks an acute large joint, it is recommended to aspirate joint fluid and then perform intra-articular glucocorticoid treatment if conditions permit.

(6) For severe acute gout attacks (VAS pain greater than or equal to 7), multiple joints or involving more than or equal to 2 major joints, 2 analgesics are recommended, such as colchicine + NSAID or colchicine + glucocorticoid.

(7) The combined use of NSAIDs and systemic corticosteroids is not recommended.

(8) When using glucocorticoids for a long time, oral gastric mucosal protectants are required, and close attention should be paid to adverse drug reactions such as cardiovascular safety, hepato-renal toxicity, gastrointestinal reactions, and osteoporosis.

Nineteenth key to curing gout: long-term uric acid-lowering treatment.

(1) After starting to take uric acid-lowering drugs, fluctuations in blood uric acid levels can cause tophi or urate crystals inside and outside the joints to dissolve, leading to repeated attacks of gouty arthritis.

(2) During the first 3-6 months of uric acid-lowering treatment, blood uric acid levels significantly decreased, and 12%-61% of patients experienced recurrent gout attacks.

(3) After 8-12 months of continued treatment, the frequency of gout attacks decreased significantly.

(4) Low-dose colchicine 0.5-1 mg/d is recommended both at home and abroad to prevent attacks for at least 3-6 months.

(5) For patients with renal insufficiency, adjust the colchicine dose according to the glomerular filtration rate.

A: Glomerular filtration rate 35-59 ml.min. Maximum dose of colchicine 0.5 mg/d

B: Glomerular filtration rate 10-34ml.min. Maximum dose of colchicine 0.5mg/once every other day.

C: Colchicine is contraindicated if the glomerular filtration rate is less than 10 ml.min.

20. Definition and treatment principles of refractory gout;

A: Definition:

(1) The serum uric acid level is still greater than or equal to 360 umol/L despite the use of conventional uric acid-lowering drugs alone or in combination for a sufficient dose and duration of treatment.

(2) Despite receiving standard treatment, gout attacks still occur more than or equal to 2 times per year.

(3) The presence of multiple and progressive tophi.

B: Treatment principles:

(1) Uric acid-lowering treatment of refractory gout with polyethylene glycol recombinant uricase preparations.

(2) For patients with refractory gout whose pain recurs repeatedly and cannot be controlled by conventional treatment, consider interleukin-1 or tumor necrosis factor@.

(3) When tophi cause local complications (infection, rupture, nerve compression) or seriously affect the quality of life, surgical treatment should be considered.

XX. Choice of uric acid-lowering drugs for patients with hyperuricemia and chronic kidney disease:

It is recommended to individualize uric acid-lowering drugs and dosages according to the stage of chronic kidney disease;

A: Febuxostat:

(1) It is recommended that the glomerular filtration rate be less than 30 ml/min. Febuxostat is the preferred uric acid-lowering drug.

(2) After oral administration, Febuxostat is mainly metabolized in the liver and excreted through both the kidneys and intestines.

(3) Compared with other uric acid-lowering drugs, it has better uric acid-lowering effect and kidney protection effect.

(4) Febuxostat still has a certain therapeutic effect on gout combined with stage 4-5 renal disease.

(5) For patients with stage 4-5 renal insufficiency, the recommended dose of febuxostat is 20 mg/d, with a maximum dose of 40 mg/d.

B: Benzbromarone:

(1) 50% of the drug is absorbed after oral administration, and the metabolites are mainly excreted through the bile duct.

(2) For patients with mild to moderate renal insufficiency, it has a good uric acid-lowering effect without causing drug accumulation and further kidney damage.

(3) It is not recommended for patients with renal insufficiency stage 4-5 and glomerular filtration rate less than 30ml.min

22. Drug selection for hyperuricemia and gout combined with hypertension:

(1) Losartan and/or calcium channel blockers are preferred.

(2) It is not recommended to use thiazides and loop diuretics alone for antihypertensive drug treatment.

23. Hyperuricemia and gout combined with hyperlipidemia (lipid metabolism disorder 67%):

(1) Hypertriglyceridemia: Firofibrate (inhibits reabsorption of uric acid in the proximal tubules of the kidney and promotes renal uric acid excretion)

(2) Hypercholesterolemia: Atorvastatin calcium (promotes renal uric acid excretion and reduces blood uric acid levels)

24. Drug selection for hyperuricemia and gout combined with diabetes:

(1) Metformin

(2) @-Glucosidase inhibitors

(3) Insulin sensitizers

(4) Dipeptidyl peptidase 4 inhibitors

(5) Sodium-glucose cotransporter 1 inhibitors

Peng Jiyun, Department of Rheumatology and Immunology, Chengdu Western Gout and Rheumatism Hospital

[Warm Tips] Follow us, there are a lot of professional medical knowledge here, revealing the secrets of surgical anesthesia for you~