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Lab test update - uric acid

Chemical pathologist Dr Berenice Lopez uses a primary care case history to discuss the clinical implications of raised uric acid levels

Chemical pathologist Dr Berenice Lopez uses a primary care case history to discuss the clinical implications of raised uric acid levels

The case

A 53-year-old man attends in a state of some anxiety. He has attended a private screening medical and among the battery of tests he has been subjected to is a blood screen. This revealed a raised uric acid of 570µmol/l.

He has a history of hypertension, for which he takes bendroflumethiazide 2.5mg a day, and he had one episode of renal colic many years ago. There is no history of gout, and he is on no other medication. His blood pressure is well controlled.

He's extremely concerned about this finding and wants to know what should be done about it.

What is the relevance of an elevated uric acid in a patient with no symptoms?

One of the problems is defining ‘elevated'. The urate level itself is actually more informative. Reference ranges tend not to be too informative because serum urate levels are not normally distributed in most populations, making them less helpful.

The solubility limit of urate in body fluids at body temperature is 420µmol/l (0.42mmol/l). This commonly defines the upper reference limit, as the risk of gout increases with increasing levels of urate greater than 420µmol/l.

Premenopausal women tend to have lower urate levels because of the uricosuric effect of oestrogen and consequently have a lower upper limit – 360µmol/l is usually quoted.

Although gout may develop in a hyperuricaemic individual at any point, two-thirds or more remain asymptomatic so allopurinol and other uricosuric drugs are not usually indicated.

Hyperuricaemia can also result in hyperuricosuria and increase the risk of uric acid and calcium phosphate or calcium oxalate stone formation. But these are more frequently seen in those with no apparent abnormality in uric acid metabolism because other factors such as urine pH play a role.

Hyperuricaemia is also associated with acute and chronic kidney disease, usually as a consequence, with levels increasing as GFR falls to less than 20ml/min. On occasion though, it may be the cause. Persistent hyperuricaemia, at levels greater than 773µmol/l in men and 595µmol/l in women, which are uncommon, may be nephrotoxic.

Serum uric acid is epidemiologically associated with hypertension, diabetes and cardiovascular disease and has also been demonstrated to be a strong independent prognostic marker in heart failure. It has also been associated with increased mortality from CVD. These associations have been observed not only with urate levels above 420µmol/l but also with levels considered to be in the normal to high range – 310-330µmol/l.

An important consideration is the possibility that serum uric acid may be a mechanism of disease. Trials to examine the effects of urate-lowering in these groups of patients are being undertaken.

Should patients with an elevated uric acid level be subjected to other biochemical tests?

Yes, assess other CV risk factors such as fasting lipid profile and glucose. Check renal and liver function. Depending on the clinical scenario, you may also want to check a FBC and film, B12 and TFTs as on occasion elevated serum urate levels may be seen in conditions such as lymphoproliferative and myeloproliferative disorders, B12 deficiency, lead exposure and hypothyroidism.

This patient has a history of renal colic. It is important to find out whether a diagnosis of renal stones has been established by imaging or stone analysis and whether there is a history of recurrent renal colic or stone disease. Assessment of renal function, including serum bicarbonate, calcium and phosphate, is important. Urinalysis to look for an acidic pH – a risk factor, urate crystals and infection are relatively simple and useful investigations.

He will need to be referred for a full metabolic evaluation if he has been a recurrent stone former.

How likely is it that his diuretic or lifestyle are contributing to his raised uric acid?

Very likely. Hyperuricaemia is a relatively common finding in patients taking loop or thiazide diuretics, particularly if they become volume depleted. Essentially, diuretics increase net urate reabsorption. Although this is not a reason to stop thiazide diuretics in low-risk patients, this man may be better off on another antihypertensive. Alternatively, you could consider adding an ACE inhibitor or ARB as these can minimise diuretic-induced increases in serum urate.

41222652Obesity and high purine and alcohol intakes can also cause hyperuricaemia. The patient should be given advice if relevant. Note that a low-purine diet can reduce serum urate levels by up to 15% and urinary excretion by rather more, so diet is important. Beer, lager, port and some wines should be avoided because they are high in purines.

But excess alcohol in itself can be a cause of hyperuricaemia so patients should be advised to stay within recommended limits. Avoidance of drugs that affect urate excretion, including low-dose aspirin, may also be helpful.

In patients who do develop gout, it is often said that the uric acid shouldn't be measured in an acute attack. Is this true? If so, how soon after the attack should it be measured?

Serum urate levels may be normal during an acute attack thus the optimal time for measurement is about two weeks after a flare resolves.

In patients who are treated with allopurinol, is there any need for serial measurement of uric acid?

Serum uric acid level should be checked on a monthly basis while establishing allopurinol dosage requirements. Once serum urate is less than 360µmol/l, uric acid and renal function should be monitored every three months. Patients with gout should really think of their uric acid level in much the same way as diabetes patients think of their HbA1c.

Dr Berenice Lopez is specialist registrar in clinical biochemistry and metabolic medicine at North Bristol NHS Trust and a part-time GP

Competing interests: None declared

For more information on the use of lab tests in primary care, go to BetterTesting.org.uk, which has 120 clinical scenarios

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