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Gout affects approximately 15% of Pacific men and 3% of Pacific women. This is a similar prevalence to that in Māori,
however five-fold more than in people of European ethnicity. Pacific peoples also have high rates of severe gout, early
onset gout, tophaceous disease and accelerated joint damage.1 A major factor in the high incidence of gout
in Pacific peoples is inherently higher levels of serum urate (hyperuricaemia). Current evidence indicates that hyperuricaemia
and gout have both a genetic and environmental basis.
A genetic basis for hyperuricaemia
Recent genetic data show that genes that encode proteins responsible for excretion of urate via the kidneys and gut
are strong risk factors for gout in Pacific peoples. A genetic variant in the SLC2A9 gene confers a greater than five-fold
increased risk for gout in Pacific peoples,2 and a genetic variant in the ABCG2 gene confers a three-fold increased
risk of gout.3 It is thought that these genetic variants reduce the ability to excrete urate, contributing
to hyperuricaemia and thus the risk of gout. This genetic information is consistent with biochemical data from the 1980s
that demonstrated reduced renal clearance of urate in Pacific peoples when compared to people of European ethnicity.
Dietary influences in hyperuricaemia with particular reference to fructose
It is well recognised that certain foods, e.g. alcohol, meat and shellfish, contribute to hyperuricaemia. Recent studies
in North America have shown that soft drinks sweetened with high fructose corn syrup, but not artificially sweetened soft
drinks, are also associated with hyperuricaemia and gout.4,5 This effect of increasing serum urate was also
seen with fruit juice and excessive consumption of fruit. Fructose is a component of refined sugar, but in contrast to
glucose, the metabolism of fructose in the blood is not regulated. Therefore fructose cannot be stored in the body, in
the way glucose is stored as glycogen in the liver. An adverse effect of the unregulated catabolism of fructose is the
production of urate in the blood, increasing the risk of gout in people who are genetically predisposed to excrete less
Patients with gout, particularly Pacific patients, should be advised to drink water, unsweetened coffee and tea, and
milk rather than fruit juices and sugar-sweetened soft drinks. Low fat dairy products such as milk have been shown to
be associated with lower serum urate levels and reduced risk of gout.6 In patients with poorly controlled gout,
excessive fruit intake should also be advised against. A healthy diet including recommended serves of fruit and vegetables
should be recommended.
High fructose consumption is also implicated in hypertension. A clinical study has shown that concurrently lowering
uric acid levels with allopurinol prevents an increase in arterial blood pressure.7 The authors of the study
postulated that excessive fructose intake also has a role in the current obesity and diabetes epidemic.8
The role of allopurinol in the management of gout
Allopurinol is the most commonly used drug for the long-term management of gout. It inhibits the enzyme xanthine oxidase,
which is responsible for the production of urate. It can be difficult to establish patients on allopurinol, as it often
precipitates gout flares. However, concurrent administration of colchicine, non-steroidal anti-inflammatory agents or
corticosteroids in the first three to six months is an effective strategy for preventing gout flares.
Sustained reduction of serum urate <0.36 mmol/L is critical for the long-term management of gout. It may take 6–12
months of serum urate levels <0.36 mmol/L before gout attacks abate. In general, creatinine clearance (CrCL) based
doses of allopurinol are used in an attempt to reduce potential adverse effects, in particular allopurinol hypersensitivity
syndrome. However, many patients fail to achieve the target serum urate (<0.36 mmol/L) with CrCL based doses.9 In
renal impairment, reducing the dose of allopurinol does not increase its safety.
The effects of increasing the dose of allopurinol above CrCL based doses in patients who fail to achieve reduction in
serum urate to <0.36 mmol/L has recently been investigated in a New Zealand based study.10 The dose of allopurinol
was gradually increased until the target serum urate was achieved. The dose of allopurinol required to reach the target
ranged from 50–400 mg above the CrCL based dose. All but one patient (34 out of 35) achieved a serum urate <0.36 mmol/L
at some stage during the study period and in 31 patients this was sustained. There were no significant adverse effects
during the twelve month study period. Although larger studies are required for confirmation of the safety of such an approach,
treating with allopurinol to achieve the target serum urate appears safe and effective.
“Treat to target”
From a practical perspective it is recommended to gradually build up to the CrCL based dose of allopurinol. If this
fails to achieve the target serum urate after four to six weeks, the dose of allopurinol should be systematically increased
until the target serum urate of <0.36 mmol/L is reached unless adverse events occur. This “treat-to-target” approach
is being increasingly practised and accepted.
Other urate lowering therapies
Other urate lowering therapies which increase the excretion of urate via the kidneys are available. Benzbromarone is
one such agent which exerts its effects through the SLC2A9 urate transporter in the kidney. Benzbromarone may be a more
effective therapy for Pacific peoples with gout who under-excrete urate, however it is not currently registered for use
in New Zealand.
For further information about the treatment of gout, see; “Gout
– hit the target”, BPJ 8 (Sept, 2007) and “Gout in the Māori
community”, BPJ 13 (May, 2008).
This article was contributed by Associate Professor Tony Merriman, Department of Biochemistry, University
of Otago, Dr Peter T Chapman, Department of Rheumatology, Immunology and Allergy, Christchurch Hospital
and Dr Lisa K Stamp, Department of Medicine, University of Otago, Christchurch. Thank you also to Dr
Fionna Bell, Clinical Director, TaPasefika Health Trust, Auckland for expert guidance in developing this article.
- Dalbeth N, Kumar S, Stamp L, Gow PJ. Dose adjustment of allopurinol according to creatinine clearance does not provide
adequate control of hyperuricaemia in patients with gout. J Rheumatol 2006;33:1646-50.
- Hollis-Moffatt JE, Xu X, Dalbeth N, et al. A role for the urate transporter SLC2A9 gene in susceptibility to gout
in New Zealand Māori, Pacific Island and Caucasian case-control cohorts. Arthritis Rheum 2009;60: 3485-92.
- Phipps-Green AJ, Hollis-Moffatt JE, Dalbeth N, et al. A strong role for the ABCG2 gene in susceptibility to gout
in New Zealand Pacific Island and Caucasian, but not Māori, case and control sample sets. Hum Mol Genet 2010;In
- Choi HK, De Vera MA, Krishnan E. Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile.
Rheumatology (Oxford) 2008;47:1567-70.
- Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National
Health and Nutrition Examination Survey. Arthritis Rheum 2007;57:109-15.
- Dalbeth N, Wong S, Gamble GD, et al. Acute effect of milk on serum urate concentrations: a randomised controlled
crossover trial. Ann Rheum Dis 2010; 69: 1677-82.
- Perez-Pozo SE, Schold J, Nakagawa T, et al. Excessive fructose intake induces the features of metabolic syndrome
in healthy adult men: role of uric acid in the hypertensive response.Int J Obes 2010;34:454-61.
- Johnson RJ, Perez-Pozo SE, Sautin YY, et al. Hypothesis: could excessive fructose intake and uric acid cause type
2 diabetes? Endocr Rev 2009;30:96-116.
- Stamp L, Chapman P. Existing and emerging therapies for acute gout and long-term urate lowering. Curr Rheumatol Rev
- Stamp L, O'Donnell J, Zhang M, et al. Using allopurinol above the dose based on creatinine clearance is effective
and safe in chronic gout, including in those with renal impairment. Arthritis Rheum 2010;[Epub ahead of print].