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Alkalinization of urine is a common adjunct to the treatment of gout, which works by changing the pH of the urine to help prevent the formation of urate crystals, thereby reducing the risk of gout attacks. Some people ask, can drugs that alkalize urine directly reduce uric acid to normal levels? Can it be used for a long time to avoid gout attacks? Let's find out!
(1) What is alkalinized urine? What is the effect of alkalizing urine on uric acid-lowering?
Alkalinizing urine, simply put, is to adjust the pH value of urine from acidic or neutral to alkaline through medication or diet.
The reason why gout alkalizes urine is because the pH of urine affects urate crystals.
Uric acid, the end product of purine metabolism, is a weak acid that can combine with sodium ions to form monosodium urate (MSU) crystals. Factors affecting the formation of MSU crystallization include pH, when the pH value is low, the solubility of MSU crystals will also be reduced, and crystal deposition is more likely to form.
The lower the urine pH, the lower the solubility of uric acid and the easier it is to crystallize and deposit
The pH of urine affects the solubility of uric acid in the urine. Studies have shown that when the pH of uric acid is 4.75, 90% of uric acid is in a crystalline state; When the urine pH is from 5.0 to 6.0, the dissolved amount of uric acid increases by a factor of 3, and when the urine pH is 6.75, 90% of the uric acid is dissolved. As we all know, most of the uric acid in our body is excreted in urine through the kidneys, and the purpose of alkalizing urine is to improve the solubility of uric acid in the urine and make it easier to excrete.
Under normal circumstances, the pH value of urine is about 4.6~8.0, and the urine pH value of gout patients may be low, which can be increased to between 6.0~6.8 by alkalinizing urine. The Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019) pointed out that the best morning urine pH value for patients with gout is 6.2~6.9, which should not be too low, which is not conducive to uric acid excretion and will increase the risk of uric acid kidney stones, but it should not be too high, and too high will increase the incidence of calcium phosphate stones.
(2) What drugs are commonly used to alkalize urine? What are the precautions?
Commonly used drugs for alkalizing urine are sodium bicarbonate, citrate, acetazolamide, etc., which will be introduced separately below.
01 / Sodium bicarbonate
Sodium bicarbonate works by providing alkaline ions to neutralize the acidic components in the urine, thus achieving the effect of alkalizing the urine. Sodium bicarbonate has a strong effect on alkalizing urine, and is inexpensive and well tolerated, and is a commonly used urine alkalizing drug for gout patients.
【Precautions】
- (1) Sodium bicarbonate is produced orally with obvious gas, and its main adverse reactions are flatulence and gastrointestinal discomfort;
- (2) Long-term use of sodium bicarbonate can lead to sodium load to promote urinary calcium excretion and increase the risk of calcium kidney stones;
- (3) Long-term use of sodium bicarbonate can lead to electrolyte imbalances, resulting in hypokalemia and metabolic alkalosis;
- (4) Improper use of sodium bicarbonate may increase the risk of congestive heart failure, liver cirrhosis and uncontrolled hypertension in patients;
- (5) The risk of heart failure will be increased when the concentration of bicarbonate in the blood is > 26mmol/L, and the risk of kidney disease will be increased when it is less than 22mmol/L. Therefore, in the process of alkalizing urine with sodium bicarbonate, the concentration of bicarbonate in the blood should be maintained at 22~26mmol/L.
Sodium bicarbonate is a commonly used medication for alkalizing urine
02 / Citrate
Citrates include sodium potassium hydrogen citrate, potassium citrate, sodium citrate, and potassium magnesium citrate. Among them, potassium citrate is more popular than sodium citrate, on the one hand, because sodium citrate can induce complications of calcium kidney stones, and on the other hand, potassium citrate not only has the effect of alkalizing urine, but also provides potassium ions, which has a protective effect on the heart.
【Precautions】
- (1) The most common adverse reactions of citrate are gastrointestinal discomfort, abdominal pain and diarrhea.
- (2) Potassium citrate can cause hyperkalemic arrhythmia, especially in elderly patients with impaired renal function, who are prone to hyperkalemia after taking potassium citrate, and can cause fatal hyperkalemic arrhythmia in severe cases.
- (3) Sodium citrate can induce complications of calcium nephrolithiasis.
- (4) The first use of citrate should check the renal function and electrolytes, acute kidney injury or chronic renal failure, severe acid-base balance disorder and liver insufficiency, patients should not use citrate.
- (5) Potassium citrate should not be combined with potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and other drugs, which will increase the risk of hyperkalemia.
- (6) During the use of prescription potassium citrate, blood potassium level and renal function should be measured.
Potassium citrate is more suitable than sodium citrate
03 / Acetazolamine
Acetazolamide is a carbonic anhydrase inhibitor that is less commonly used as an adjunct to increasing uric pH than sodium bicarbonate and citrate. The pharmacology of acetazolamide is to alkalize urine by blocking the reabsorption of bicarbonate and inhibiting the excretion of hydrogen ions.
【Precautions】
- (1) Acetazolamide can be used as an option when gout patients are unable to achieve the expected urine pH value, or when they need a large dose of alkaline to cause gastrointestinal adverse reactions.
- (2) For patients with urinary tract stones who take potassium citrate but the urine pH value cannot reach 6.5, the addition of acetazolamide can effectively increase the urine pH value to 6.5.
- (3) Acetazolimide will reduce urinary citrate excretion and promote urinary calcium excretion, increasing the risk of calcium phosphate stone formation.
- (4) Acetazolimide can cause metabolic acidosis, resulting in hypokalemia.
Acetazolilamide is mainly used as an adjunct to alkalinize urine
(3) Can gout patients always use drugs that alkalinize urine?
In fact, when the precautions for sodium bicarbonate were introduced above, you should be able to guess that drugs that alkalize urine cannot be used for a long time. The reason is very simple, the pH value of urine suitable for uric acid excretion is 6.2~6.9, and too high or too low will cause harm to the body.
Moreover, the main effect of alkalizing urine is not to directly reduce uric acid in the blood, but to increase the solubility of urate in the urine by increasing the pH value of the urine, promoting the excretion of uric acid from the kidneys, and reducing the deposition of urate crystals in the kidneys and urinary system, and preventing the occurrence of urinary tract stones.
To put it simply, alkalizing urine can only assist in lowering uric acid, but does not have a direct uric acid-lowering effect. It can be used as an adjunct to urate-lowering therapy, but not on a stand-alone basis for the treatment of uric acid.
Alkalinization of urine is not a substitute for urate-lowering therapy
When do people with gout need medications that alkalinize their urine?
Generally, at the beginning of urate-lowering therapy, alkalinized urine therapy is taken at the same time; Urine alkalinization is also recommended when the urine pH is < 6.0, and must be accompanied by alkalinization in patients who are taking drugs that promote uric acid excretion, such as benzbromarone.
When should alkalinization urine therapy be stopped?
When the urine pH value reaches and is maintained at 6.2~6.9, or the patient's uric acid level and gout symptoms are effectively controlled, then the use of alkalinizing urine drugs can be gradually reduced or stopped. In short, urine pH monitoring and other related monitoring should be done during the alkalinization of urine, and it should not be used arbitrarily or excessively, let alone use drugs that alkalinize urine all the time.
Eating more fresh vegetables also has the effect of alkalizing urine and promoting uric acid excretion
In fact, there is another way to alkalize urine, and that is dietary modification. The best way is to eat more fresh vegetables (fruits should consider the influence of fructose), fresh vegetables also have a certain alkalizing urine, can promote uric acid excretion, has a protective effect on gout, it is recommended to consume no less than 500g per day, more than half of which are dark vegetables.