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There is a common perception that gout is well understood and easily managed, but we continue to see patients with refractory arthritis, tophi, and drug complications that we would hope to avoid. A small number of investigators continue to study gout. Here we present some recent articles addressing aspects that may help us all improve our management.

Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES

Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kimmen (J Rheumatol, 2000) (1).

This population survey conducted in 1991–1992 studied residents in Kin-Hu, Taiwan, aged ≥30 years. The study's aim was to assess the prevalence of hyperuricemia and hyperuricemia-associated gout.

Hyperuricemia was defined as uric acid ≥7 mg/dl for men and ≥6 mg/dl for women. Gout was clinically diagnosed by a senior rheumatologist based on the patient's history and examination according to the clinical criteria of Wallace.

The mean serum uric acid (SUA) levels were 6.14 ± 1.43 mg/dl for men and 4.7 ± 1.33 mg/dl for women. The prevalence of hyperuricemia was 25.8% in men and 15% in women. The prevalence of gout among hyperuricemic subjects was 11.5% for men and 3% for women. Hyperlipidemia was found to be a risk factor in young adults (ages 30–39 years). Hyperuricemia was found to be associated with a cluster of disorders associated with coronary heart disease, such as hyperlipidemia, hypertension, obesity, and diabetes mellitus in middle-aged people (ages 40–59 years). Alcohol consumption in middle-aged men and menopause in women were independent risk factors. The prevalence of hyperuricemia was more than twice as high in women aged 50–59 as compared with those aged 40–49, whereas the SUA in men remained stable with advancing age. Impaired renal function and use of diuretics were independent risk factors in the elderly (age ≥60 years).

The risk factors for gout in the general population and among the subjects with hyperuricemia were uric acid level, alcohol consumption, and obesity. In this study, alcohol consumption and central obesity were found to be independent predictors of gout among hyperuricemic patients irrespective of SUA level. Therefore avoiding diuretic therapy, weight gain, and alcohol consumption may lead to a decrease in gouty arthritis.

Should a low purine diet be the only dietary emphasis for patients with gout?

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES

Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum and lipoprotein levels in gout: a pilot study (Ann Rheum Dis, 2000) (2).

Insulin resistance has been increasingly implicated in the pathogenesis of gout. Hyperuricemia is associated with high fasting insulin levels. Insulin normally stimulates the reabsorption of organic anions, such as urate. Insulin resistance and hyperinsulinemia cause hyperuricemia. Insulin resistance is associated with decreased urinary uric acid clearance and, therefore, increased SUA concentrations. Current dietary recommendations for gout include limitation of purine, protein, and alcohol as well as weight reduction. The study investigated whether weight loss through limitation of calorie and carbohydrate intake, together with increased intake of protein and replacement of saturated fat by unsaturated fat, which is beneficial in insulin resistance, will have SUA- and lipid-lowering effects in patients with gout.

Thirteen Caucasian men with gout were studied. The number of gouty attacks over the previous 4 months was recorded, as was body mass index. A fasting lipid profile and SUA level were taken at enrollment. None of the patients were taking hypouricemic agents. Dietary intervention was designed to comprise 1,600 kcal/day with 40% energy derived from carbohydrates, 30% from protein, and 30% from fat. After the initial visit, patients were evaluated at 4, 10, and 16 weeks. At each visit, the number of gouty attacks was recorded and fasting SUA and lipid profile were taken.

After 4 months of dietary intervention, mean SUA levels decreased significantly (by 18%) in all 13 gouty patients. This was accompanied by a 67% reduction in the frequency of monthly gouty attacks.

The authors recommend reevaluation of the current dietary recommendations for patients with gout. They advocate limitation of carbohydrate intake, an increased proportional intake of protein, and the use of unsaturated fat, because they all enhance insulin sensitivity and therefore may promote a reduction in SUA. Limitation of alcohol use and excessive purines would still be important, as would more studies on the details of diet.

Aspirin affects serum uric acid levels

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES

The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients (Arthritis Rheum, 2000) (3).

Current consumption of aspirin in the US is estimated to be 10,000–20,000 tons per year. It is often taken as an over-the-counter remedy. Aspirin is known to have a bimodal effect on renal handling of uric acid. High dosages (>3 gm/day) are uricosuric, whereas low dosages (1–2 gm/day) cause uric acid retention. The effects of mini-dose aspirin (<0.5 mg/day) on this bimodal phenomenon have not been studied.

The role of aspirin in uric acid handling was examined in this prospective study by Caspi et al. The effects of mini-dose aspirin (75–325 mg/day) on renal function and uric acid handling in elderly patients were assessed. Forty-five elderly inpatients treated with increasing dosages of daily mini-dose aspirin for 3 weeks (75 mg/day, 150 mg/day, and 325 mg/day for weeks 1–3, respectively) and none for the fourth week were monitored for the influence of the drug on their serum and urine creatinine and uric acid concentrations.

A 6.2% increase in the mean SUA level was observed in parallel to a 22.8% decrease in the mean uric acid clearance rate during the first week of mini-dose aspirin treatment (75 mg/day). During the following 2 weeks, although the aspirin dose was doubled twice, SUA concentrations and uric acid clearance rates gradually returned to near-baseline levels, and by the third week (325 mg/day) the differences from baseline were not statistically significant.

Aspirin (even in a mini-dose) has the potential to cause significant changes in renal function and uric acid handling within 1 week of treatment in elderly patients (without known renal disease, hyperuricemia, or gout) hospitalized for a variety of reasons. It also caused mild impairment of creatinine clearance that persisted for more than 1 week after discontinuation of the drug. Uric acid excretion gradually returned to near baseline levels, even after dosages were increased slightly (150 mg/day and 325 mg/day). These doses were well below uricosuric levels. Concomitant diuretic therapy and low serum albumin seem to increase the susceptibility to these side effects.

This study shows that mini-dose aspirin significantly changes renal function and uric acid handling. Aspirin at dosages of 75–325 mg/day was found to impair renal function and uric acid handling in elderly inpatients. Given the widespread use of mini-dose aspirin, especially among the elderly, clinicians should be aware of these changes and encourage or consider further studies clarifying the underlying pathophysiology responsible for these changes.

Treatment of gout in transplant recipients

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES

Post cardiac transplantation gout: incidence of therapeutic complications (J Heart Lung Transplant, 2000) (4).

Gout is a common problem among transplant patients. In cardiac transplant recipients, the likelihood of developing gout within 8 years after cardiac transplantation was 31%. Transplant recipients are exposed to cyclosporine, which impairs handling of uric acid. Cyclosporine is thought to impair the renal clearance of uric acid in 2 major ways: inhibition of urate secretion in the proximal tubule and intrarenal vasoconstriction leading to decreased glomerular perfusion and thus to decreased filtered urate load. Concomitant renal function compromise and/or diuretic therapy also play a role in hyperuricemia in these patients.

Two hundred charts of patients who had undergone orthotopic cardiac transplantation before July 1998 were reviewed. Forty-three patients had a history of gout before cardiac transplantation. Of these, 19 developed recurrent gout following transplantation. The likelihood of developing gout at 6 years following cardiac transplantation was 54% in patients with a prior history of gout and 19% with no prior history of gout (P < 0.001). Recurrent episodes and tophi occurred in 55% of patients with a prior history of gout, and 24% in patients with no prior history.

Acute attacks of gout were treated with colchicine, nonsteroidal antiinflammatory drugs, and systemic and intraarticular corticosteroids. Chronic suppression of gouty flares was mainly achieved using colchicine, with or without urate-lowering agents.

Severe adverse drug reactions are common in cardiac transplant recipients. In this study, 25% of the patients treated with allopurinol (even with reduction in doses of azathioprine and allopurinol) developed pancytopenia and required hospitalization. Relatively short courses of colchicine in the presence of only mildly impaired renal function lead to development of neuromyopathy in 16% of cardiac transplant recipients. Corticosteroids (both intraarticular and systemic) were under-used and the authors state that short courses of corticosteroids can be used safely.

Gout in chronic renal failure

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES

Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients? (Nephrol Dial Transplant, 2000) (5).

Despite prolonged and severe hyperuricemia, gouty arthritis is considered to be rare in end-stage renal disease (ESRD). Monosodium urate (MSU) crystals interact with monocytes, neutrophils, and endothelial cells to produce inflammatory reactions associated with acute synovitis. Within hours after incubation with MSU crystals, monocytes produce proinflammatory cytokines. Monocytes exposed to MSU crystals secrete interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNFα). This study investigates whether differences in secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be an explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls.

Thirteen patients with ESRD on hemodialysis treatment, 6 ESRD patients not yet on dialysis, and age- and sex-matched controls were examined. Monocytes purified from peripheral blood mononuclear cells were incubated for 18 hours in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS), and medium alone. The supernatants were studied for the presence of IL-1β, IL-6, and TNFα using cytokine-specific enzyme-linked immunoabsorbent assays.

Monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. Monocytes from patients with ESRD produced significantly lower amounts of IL-1β, IL-6, and TNFα after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on hemodialysis and chronic renal failure patients not yet on dialysis. This correlates with the suggestion that ESRD induced a clinical state of immune deficiency.

Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study(J Clin Rheumatol, 1999) (6).

Renal insufficiency is common in patients with gout. Aging, hypertension, vascular disease, and intrinsic renal diseases are variables that contribute to renal impairment in gouty patients. Proper control of hyperuricemia is important in gout to prevent recurrence of gouty attacks. This study describes an open, randomized, actively controlled, comparative trial in patients with a creatinine clearance of 20–80 ml/minute/1.73 M3. Patients were randomized to take benzbromarone (100–200 mg/day) or allopurinol (100–300 mg/day). The reduction of serum uric acid was greater with benzbromarone as compared with allopurinol treatment. Of patients taking allopurinol, 38% did not achieve optimal SUA levels during therapy, although recommended dosages according to creatinine clearance were prescribed but 94% of patients taking benzbromarone showed optimal control of SUA. A significant reduction in gouty attacks and tophi was seen after proper control of SUA levels (<6 mg/dl).

REFERENCES

  1. Top of page
  2. Nonpharmacologic treatment: avoidance of factors contributing to development of gouty attacks
  3. Should a low purine diet be the only dietary emphasis for patients with gout?
  4. Aspirin affects serum uric acid levels
  5. Treatment of gout in transplant recipients
  6. Gout in chronic renal failure
  7. REFERENCES
  • 1
    Lin KC, Lin HY, Chou P. Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kimmen. J Rheumatol 2000; 27: 104550.
  • 2
    Dessein PH, Shipton AE, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum and lipoprotein levels in gout: a pilot study. Ann Rheum Dis 2000; 59: 53943.
  • 3
    Caspi D, Lubart E, Graff E, Habot B, Yaron M, Segal R. The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients. Arthritis Rheum 2000; 43: 1038.
  • 4
    Wluka AE, Ryan PF, Miller AM, Richardson M, Bergin PJ, Page JL, et al. Post cardiac transplantation gout: incidence of therapeutic complications. J Heart Lung Transplant 2000; 19: 9516.
  • 5
    Schreiner O, Wandel E, Himmelsbach F, Galle PR, Marker-Hermann E. Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients? Nephrol Dial Transplant 2000; 15: 6449.
  • 6
    Perez-Ruiz F, Calabozo M, Fernandez-Lopez J, Herrero-Beites Ana, Ruiz-Lucea E, Garcia-Erauskin G, et al. Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. J Clin Rheumatol 1999; 5: 4955.