Correspondence

Management of Gout

N Engl J Med 1996; 334:1543-1544June 6, 1996

Article

To the Editor:

Emmerson's review of the management of gout (Feb. 15 issue)1 contains much useful information, but it also includes several arguable points. In their classic studies Gutman and Yü found that the excretion rate of urate in patients with gout was “almost invariably” within the normal range.2 Thus, it is wrong to suggest that “decreased urinary excretion of urate often contributes to hyperuricemia”1 and that measurements of urate clearance are clinically useful.

Their studies led Gutman and Yü and many other early workers to conclude that kidney changes were “the result and not the cause” of hyperuricemia. Subsequent work, however, clearly showed that in patients with gout the serum urate concentration had to be an average of 1.7 mg per deciliter higher than in normal subjects to achieve the same rate of urate excretion.3 Thus, inefficient urate excretion underlies the great preponderance of clinical hyperuricemia. This defect is poorly characterized by single measurements of either urate clearance or fractional excretion.

Detection of increased urate excretion is a worthwhile goal, but Emmerson's recommendation of two 24-hour urine collections separated by one week of dietary purine restriction will be burdensome for most patients. It makes better sense first to screen out the overwhelming majority of patients with hyperuricemia who excrete normal amounts of urate on self-selected diets by measuring urate and creatinine in serum and spot, mid-morning urine samples and calculating urate excretion normalized to a glomerular filtration rate of 100 ml per minute.4 Purine-restricted diets and 24-hour urine collections need be ordered only in those unusual patients in whom the excretion rate in spot urine samples is high.

Peter A. Simkin, M.D.
University of Washington, Seattle, WA 98195

4 References

1
Emmerson BT. The management of gout. N Engl J Med 1996;334:445-451
Full Text | Web of Science | Medline

2
Gutman AB, Yu TF. Renal function in gout. Am J Med 1957;23:600-622
CrossRef | Web of Science | Medline

3
Simkin PA. Uric acid excretion in patients with gout. Arthritis Rheum 1979;22:98-99
CrossRef | Medline

4
Simkin PA, Hoover PL, Paxson CS, Wilson WF. Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples. Ann Intern Med 1979;91:44-47
Web of Science | Medline

To the Editor:

In his review, Emmerson accurately notes that colchicine is “less favored now than in the past” because of its slow onset of action and frequent gastrointestinal side effects. However, he fails to mention the other very important factor relegating colchicine therapy for patients with gout to the past. Because colchicine interferes with neutrophil phagocytosis and chemotaxis, it is most effective when started very soon after the onset of an attack of gouty arthritis, before these factors have contributed much to the articular inflammatory process, and the beneficial effect of colchicine declines progressively the longer treatment is delayed.1,2 In contrast, the efficacy of nonsteroidal antiinflammatory drugs or glucocorticoids does not decline if therapy is delayed.

Jeff Sarkozi, M.D.
University of California, Irvine, Orange, CA 92668

2 References

1
Wallace SL. Colchicine. Semin Arthritis Rheum 1974;3:369-381
CrossRef | Medline

2
Fox IH, Kelley WN. Management of gout. JAMA 1979;242:361-364
CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Emmerson replies:

To the Editor: The renal handling of urate in gout has been debated for decades. Certainly, there is overlap between urate-clearance values in patients with gout and normal subjects, but those with urate clearances of 6 to 7 ml per minute are more likely to have hyperuricemia after a purine load than those with clearances of 12 to 14 ml per minute. Indeed, in his letter and his article,1 Simkin indicates that the renal clearance of urate must be lower in patients with gout (urate excretion rate ÷ serum urate + 1.7) than in normal subjects (urate excretion rate ÷ serum urate). I see little difference between my statement that “decreased urinary excretion of urate often contributes to hyperuricemia” and his statement that “inefficient urate excretion underlies the great preponderance of clinical hyperuricemia.”

The assessment of renal handling of urate is part of a simple series of investigations that also provide information about urate production, renal function, urine flow, and the contribution of dietary purine intake to serum and urine urate. It thereby provides more information than analysis of a spot urine sample or calculation of the ratio of serum urate to creatinine. When one is considering a potentially life-long treatment, a moderate level of investigation is surely justified, and it can help the patient come to terms with the fact that management may involve lifestyle modification in addition to taking medication.

Sarkozi is correct in emphasizing that colchicine, like most medications for acute gout, is more effective if given early. However, he is wrong in implying that colchicine no longer has a role in acute gout. Publications on the clinical usefulness of colchicine in gout continue to appear regularly,2 and although it may no longer be the drug of first choice in an otherwise healthy patient, there are still many complicated cases of acute gout in which it is useful and may even be the drug of choice.

Bryan T. Emmerson, M.D., Ph.D.
Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia

2 References

1
Simkin PA. Uric acid excretion in patients with gout. Arthritis Rheum 1979;22:98-99
CrossRef | Medline

2
Evans TI, Wheeler MT, Small RE, Breitbach SA, Sanders KM, Roberts WN. A comprehensive investigation of inpatient intravenous colchicine use shows more education is needed. J Rheumatol 1996;23:143-148
Web of Science | Medline

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