Long-term use of furosemide, uric acid 618.7μmol/L, see here for the treatment method!

*It is only for medical professionals to read for reference.
Do you want to treat or stop the drug? Just look at it! Let's look at a case first: patient, female, 82 years old
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In the past 2 years, there was no obvious cause for repeated lower extremity edema, pitting edema, and nighttime paroxysmal dyspnea and orthopedic breathing
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Long-term use of furosemide, warfarin, benazepril and metoprolol for 2 years
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In the past 2 weeks, the patient complained of the recurrence of the above symptoms and a noticeable decrease in urine output
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After admission, he was given symptomatic and supportive treatments such as diuresis, heart strengthening, and vasodilation
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Furosemide was pumped with a 140 mg micro pump for diuresis.
On the third day after admission, the blood uric acid and creatinine were 587.
6 μmol/L and creatinine 99.
5 μmol/L.
Other symptoms of hyperuricemia were not described, and no corresponding treatment was given
.

On the 10th day after admission, the blood uric acid was 618.
7 μmol/L.
He was diagnosed with hyperuricemia.
On the next day, he was given benzbromarone 50 mg orally and once a day for lowering uric acid treatment.
The patient's condition improved and was discharged one week later
.

Analysis: The patient's blood uric acid was 587.
6 μmol/L and 618.
7 μmol/L, both >420 μmol/L.
The patient was asked if he had no previous clinical symptoms of hyperuricemia and was diagnosed as asymptomatic hyperuricemia
.

Furosemide is a potent diuretic.
While diuretic, it can increase the reabsorption of uric acid in the proximal tubules and reduce the secretion of uric acid in the renal tubules, which can lead to increased blood uric acid levels.
Special attention should be paid to long-term use
.

Therefore, when furosemide is used clinically, the monitoring of the patient's blood uric acid level should be strengthened
.

 1.
Four types of diuretics commonly used clinically Diuretics act on the kidneys, increase the excretion of solute and water, and produce diuretics
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Clinically, it is mainly used for the treatment of edema caused by various reasons such as heart failure, renal failure, nephrotic syndrome and liver cirrhosis.
It can also be used for the treatment of non-edematous diseases such as hypertension, kidney stones and hypercalcemia
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The diuretics commonly used in clinical practice can be divided into 4 categories according to their sites of action (Table 1)
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Table 1 Classification of commonly used clinical diuretics 2.
Focus on diuretic-induced hyperuricemia or gout.
From Table 1, we can see that in addition to loop diuretics can cause hyperuricemia, thiazide diuretics also have hyperuricemia Adverse reactions
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Although hyperuricemia is relatively common in patients with long-term use of loop diuretics or thiazide diuretics, and may even cause new onset of gout, or quickly cause relapse in patients with gout, the incidence of clinically induced gout is low , About 3%
.

There are two possible mechanisms for diuretics to induce hyperuricemia: 1.
Diuretics directly promote the reabsorption of urate in the proximal convoluted tubule; 2.
Insufficient volume caused by diuretics indirectly promote the reabsorption of urate in the proximal convoluted tubule
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Studies have pointed out that the degree of urate retention caused by diuretics is dose-dependent, that is, the higher the dose of diuretics, the greater the probability of inducing hyperuricemia
.

 ▎Asymptomatic hyperuricemia or gout induced by diuretics, stop or keep diuretics? The diagnosis of hyperuricemia or gout is not necessarily an indication for discontinuation of diuretics, especially when diuretics are needed to treat edema, such as in patients with heart failure
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However, in the treatment of hypertension, if other suitable alternative drugs can be used to control blood pressure economically and effectively, such as the use of ACEI or CCB, diuretics can be discontinued
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 ▎Asymptomatic hyperuricemia induced by diuretics, cure or not? There are different opinions on the drug treatment of patients with asymptomatic hyperuricemia in different countries
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European and American guidelines are mostly not recommended, while Asian countries such as Japan and China tend to take a positive attitude
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The results of multiple observational studies have shown that hyperuricemia is related to the occurrence and development of various diseases.
For every 60 μmol/L increase in blood uric acid, the relative risk of hypertension increases by 1.
4 times, and the risk of new-onset diabetes increases by 17%.
The risk of death from coronary heart disease increased by 12%
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A 2019 multicenter prospective randomized controlled study (FREED) showed that febuxostat intervention in asymptomatic hyperuricemia patients can significantly reduce the incidence of cardiovascular and cerebrovascular adverse events and delay the progression of renal insufficiency
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Therefore, the "Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019)" recommends that patients with asymptomatic hyperuricemia initiate uric acid-lowering drug therapy when the following conditions occur: blood uric acid level ≥540 μmol/L; blood uric acid level ≥480 μmol /L and one of the following comorbidities: hypertension, abnormal lipid metabolism, diabetes, obesity, stroke, coronary heart disease, cardiac insufficiency, uric acid nephrolithiasis, renal impairment (≥CKD stage 2); no comorbidities It is recommended that blood uric acid be controlled at <420 μmol/L; it is recommended to control it at <360 μmol/L with comorbidities
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▎Asymptomatic hyperuricemia induced by diuretics, the drug treatment selection guide recommends allopurinol or benzbromarone as the first-line medication for lowering uric acid in patients with asymptomatic hyperuricemia.
A sufficient amount of single drug and a full course of treatment are used to treat blood uric acid For patients who have not yet reached the standard, the combined application of two uric acid-lowering drugs with different mechanisms of action may be considered
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 ▎Reduce the increase in plasma urate concentration caused by diuretics.
What are the benefits of Losartan? For patients with heart failure or high blood pressure, if you need to use ARB while using diuretics, you can choose Losartan because it may have a more direct uric acid excretion effect, thereby inhibiting the reabsorption of urate and reducing plasma The role of urate concentration
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Other drugs in this category such as irbesartan and candesartan have not been found to have the effect of lowering uric acid
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 3.
Prevention of other typical adverse reactions of diuretics▎Pay attention to monitoring body fluid and electrolyte balance.
Whether it is potassium excretion diuretics or potassium sparing diuretics, attention should be paid to monitoring the patient’s electrolyte level to prevent hypokalemia, high potassium, low magnesium or Hyponatremia
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The occurrence of hypokalemia is dose-related, and patients with hypokalemia or hypokalemia tendency should pay attention to supplementing potassium salts or adding potassium-sparing diuretics
.

If hyperkalemia occurs during the application of potassium-sparing diuretics, the drug should be stopped immediately
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▎Regular monitoring of renal function, blood sugar, blood lipids, and blood uric acid levels.
Hypokalemia caused by diuretics may reduce the sensitivity of diabetic patients to insulin, thereby causing blood sugar to rise
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▎Patients allergic to sulfa drugs, the choice of diuretics is particular because some diuretics such as furosemide, bumetanide, torasemide, hydrochlorothiazide, indapamide and acetazolamide contain sulfonamide groups in their chemical structures Patients who are allergic to sulfonamides may have cross-allergic reactions.
Etonic acid that does not contain a similar structure to sulfonamides can be used
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▎Avoid simultaneous use of loop diuretics and other ototoxic drugs.
Ototoxicity often occurs in loop diuretics, and rapid intravenous injection is more likely to occur than oral administration
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If the patient has renal insufficiency or combined use of other drugs that may cause ototoxicity, such as aminoglycosides, the risk of ototoxicity will increase, and the combined use should be avoided
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Among loop diuretics, etanyl acid has the highest ototoxicity and can cause permanent deafness.
Bumetanide has the least ototoxicity.
Bumetanide should be used for hearing defects and acute renal failure
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▎Use loop diuretics and thiazide diuretics.
Be aware that anti-loop diuretics and thiazide diuretics may cause photosensitivity.
When using it, you should pay attention to sun protection or use a sunscreen with a sun protection index (SPF)> 15
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▎Take potassium-sparing diuretics during or after meals.
Potassium-saving diuretics should be taken during or after meals to reduce gastrointestinal adverse reactions and improve bioavailability
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 References: 1.
Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019)[J].
Chinese Journal of Endocrinology and Metabolism, 2020,36(1):1-13.
2.
Yang Baofeng, Chen Jianguo.
Pharmacology (9th edition).
People Health Publishing House.
3.
Manolis AJ, Grossman E, Jelakovic B, et al.
Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension.
Losartan Trial Investigators.
Clin Ther 2000; 22:1186.
4.
Tikkanen I, Omvik P, Jensen HA.
Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension.
J Hypertens 1995; 13:1343.
5.
Würzner G, Gerster JC, Chiolero A, et al.
Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout.
J Hypertens 2001; 19:1855.