Don't start uric-acid-lowering drugs just because a checkup found high uric acid when you've never had gout pain

Cost

Free, and you save the long-term drug cost and the cost of regular rechecks, and avoid the risk of taking a drug you didn't need.

What you get

The American College of Rheumatology's 2020 gout guideline addresses asymptomatic hyperuricemia. This means blood uric acid >6.8 mg/dL, with no earlier gout attack and no tophi under the skin. The guideline conditionally recommends that these people not start any uric-acid-lowering drug. The drugs include allopurinol, febuxostat and probenecid. The certainty of the evidence was rated “high.” A footnote below the table states that “calculated by attributable risk, 24 patients must be treated for 3 years to prevent one gout attack.” The CKD-FIX randomized controlled trial enrolled 363 people. They had stage 3 or 4 chronic kidney disease, no history of gout, but a risk of getting worse. One group took 100–300 mg of allopurinol a day and one took a placebo. The trial ran for 104 weeks. eGFR is a measure of kidney function, in mL/min/1.73 m². One group changed by -3.33 a year (95% CI -4.11 to -2.55). The other changed by -3.23 a year (-3.98 to -2.47). The two differed by -0.10 (-1.18 to 0.97), P=0.85, so kidney function fell at the same speed. Serious adverse events were 46% versus 44%. The PERL randomized controlled trial enrolled 530 people with type 1 diabetes and early to moderate diabetic kidney disease, gave them allopurinol for 3 years, and then stopped it for 2 months to wash out the drug's effect. Allopurinol did lower blood uric acid from 6.1 to 3.9 mg/dL. But after stopping, the two groups' kidney measure GFR differed by only 0.001 mL/min/1.73 m². The plausible range for that difference is 95% CI -1.9 to 1.9, P=0.99. Albumin leaking into the urine was actually 40% higher in the allopurinol group (0 to 80). It looks like a good deal because “a number over the limit should be pushed down by a pill” is too smooth an intuition

Notes

What is being ruled out is “starting lifelong uric-acid-lowering drugs without ever having had an attack,” not that high uric acid doesn't matter. The same guideline also lists exceptions. In the following situations you can consider starting. One is a first attack together with stage 3 or higher chronic kidney disease. Two is blood uric acid >9 mg/dL (about 535 µmol/L). Three is a history of urinary tract stones. People who have already had an attack, people with tophi, and people whose imaging shows bone already eroded should take the drug. For details, see §16.9 (take uric-acid-lowering drugs long term once gout is diagnosed). About 7.4% of Han Chinese carry a genotype called HLA-B*5801, versus only 0.7% of white people. People with this type who take allopurinol are more likely to get a deadly severe drug rash, and the risk of hypersensitivity syndrome in Asians is 3 times that in white people. This is a drug you can hold off on in the first place, so there is no need to take this extra risk. Before you really start, get tested for this genotype first; see §16.9 (take uric-acid-lowering drugs long term once gout is diagnosed). The two kidney trials were done in patients with chronic kidney disease and with type 1 diabetes, and cannot be generalized directly into “high uric acid is completely harmless to the kidneys.” What they rule out is only the one practice of “using a drug to lower uric acid to protect the kidneys”

Evidence grade

A : Specific numbers from meta-analyses, large cohorts or randomized trials; for law and policy, the statute or official text.

Sources

1. FitzGerald JD, Dalbeth N, Mikuls T, et al. (2020). 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care & Research, 72(6), 744-760（表 1 及其脚注）. https://doi.org/10.1002/acr.24180
2. Badve SV, Pascoe EM, Tiku A, et al. (2020). Effects of Allopurinol on the Progression of Chronic Kidney Disease. New England Journal of Medicine, 382(26), 2504-2513. https://doi.org/10.1056/NEJMoa1915833
3. Doria A, Galecki AT, Spino C, et al. (2020). Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. New England Journal of Medicine, 382(26), 2493-2503. https://doi.org/10.1056/NEJMoa1916624

Translated from the Chinese original. Original book, section 6, tip 19. Content may be out of date and rules differ by place. When you actually deal with an agency, a doctor or a court, follow what local officials, doctors and lawyers tell you. Disclaimer