How do loop diuretics cause gout

These patients should also be monitored for symptoms that might precede the onset of gout. Approximately two out of three patients with drug-induced hyperuricaemia will remain asymptomatic [ 24 ]. In drug-induced asymptomatic hyperuricaemia, especially with diuretics, treatment to control serum uric acid levels is rarely required.

However, gouty episodes in patients with a personal or family history of established gout may be aggravated by diuretic therapy in hypertensive patients.

When gout develops the decision to continue therapy needs to be individualized, and so too does a decision to initiate allopurinol or a uricosuric drug [ 7 ].

In drug-induced symptomatic hyperuricaemia and gout, management includes the identification of offending drugs and the institution of appropriate anti-hyperuricaemic agents. Withdrawal of the offending drug should be based on an assessment of the benefit—risk ratio.

When alternative therapy is available, the offending drug may be replaced by a drug that does not cause hyperuricaemia. However, in certain cases, the offending drug is necessary. For example, the use of low-dose aspirin for prevention of cardiovascular disease should not be suspended for patients with gout. Close monitoring of serum uric acid when an individual is taking low-dose aspirin may help to avoid the risk of gout attacks. However, allopurinol or uricosuric agents may be necessary in some cases of aspirin-induced gout [ 54 ].

In hypertensive patients controlled on one or two medications with acute thiazide-induced gout, the reduction of the dose of thiazide rather than its discontinuation is an appropriate option because drug-induced hyperuricaemia is dose-related [ 8 ]. In hypertensive patients controlled on three or more medications thiazide continuation with dose reduction or pharmacological anti-hyperuricaemic therapy, that is, allopurinol, should be considered. Treatment of ciclosporin-induced acute attacks may be difficult since interactions with NSAIDs may lead to enhanced renal toxicity.

Colchicine, if prescribed in these acute attacks, should also be used cautiously and the dose reduced. Corticosteroids are an effective alternative to colchicine. In patients who develop ciclosporin-induced hyperuricaemia and gouty arthritis with tophi, benzbromarone, a uricosuric agent, may be useful. It should be initiated at a low dose and gradually increased, and liver function should be monitored closely.

Allopurinol is also a useful alternative in these patients. Interestingly, the normalization of uric acid levels by allopurinol or benzbromarone reduced the tubulointerstitial disease and arteriolar hyalinosis induced by ciclosporin [ 89 ]. Ciclosporin and tacrolimus withdrawal may be considered for transplant patients with recurrent, severe gout that cannot be managed safely or effectively [ 90 ].

The cornerstone management of TLS is prevention. Prevention strategies may also include hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients [ 91 ]. For nicotinic acid-induced hyperuricaemia, allopurinol is usually used when therapy is indicated. Nicotinic acid inhibits the effect of uricosuric drugs such as sulfinpyrazone and the latter should be avoided.

Pyrazinamide-induced hyperuricaemia can be managed by observation and does not require withdrawal of treatment. It can be also controlled with allopurinol.

However, paradoxical increase in uric acid level with allopurinol use in pyrazinamide-induced hyperuricaemia has been reported [ 92 ]. Allopurinol was shown to increase plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion [ 92 , 93 ]. Aspirin may prevent hyperuricaemia and the arthralgia associated with pyrazinamide therapy.

Hyperuricaemia due to ethambutol was reversed with probenicid, sulfinpyrazone or allopurinol. The latter, increases the serum level of theophylline and therefore the serum level of theophylline should be carefully monitored when allopurinol is added to a hyperuricaemic patient who is under this treatment [ 94 ].

However, benzbromarone and probenecid do not seem to interfere with the theophylline serum level. In conclusion, drug-induced hyperuricaemia and gout present an emergent and increasingly prevalent problem in clinical practice. Drugs raise serum uric acid level by various mechanisms. Patients receiving these drugs should be encouraged to maintain adequate hydration and have their uric acid levels monitored.

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Br J Clin Pharmacol. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. Lancet Diabetes Endocrinol. Download references. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. You can also search for this author in PubMed Google Scholar. All named authors have contributed directly to the work with substantial contributions to conception and design and to drafting and revising the article critically for important intellectual content and final approval of the version to be published.

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Published : 26 October Anyone you share the following link with will be able to read this content:. Increased risk for gout is among the potential adverse effects of thiazides that clinicians should consider when choosing first-line antihypertensive drugs.

Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study. Arthritis Rheum Jan; Arthritis Rheum Jan Diuretic use raised risk for gout by several percentage points. Comment According to these results, diuretic use raises risk for gout by several percentage points in hypertensive patients. October 16,