Low Urate Limits for Gout Questioned in

Study
Laird Harrison
August 18, 2022
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Lower limits on serum urate levels applied in gout management may be based on
a misreading of data on mortality risks, researchers say.
Low urate levels may not in themselves pose a risk of death but may be a sign of
some other illness, said Joshua Baker, MD, MSCE, associate professor of
rheumatology and epidemiology at the University of Pennsylvania in
Philadelphia.

Dr Joshua Baker
“It points us towards being more reassured that we can be aggressive in treating
gout without a concern about long-term effects for our patients,” he
told Medscape Medical News. He and colleagues published their findings
online Aug. 16 in Arthritis & Rheumatology.
Previous research has linked high levels of urate with excessive fat and low
levels of urate with loss of skeletal muscle mass. And epidemiologic studies have
shown a U-shaped relationship between urate levels and mortality, suggesting
that very high and very low levels of urate could be harmful.
Based on this correlation, and the theory that urate could have antioxidant
benefits, some professional societies have recommended not lowering urate
levels below a defined threshold when treating gout. For example, the European
Alliance of Associations for Rheumatology has recommended a lower limit of 3
mg/dL.
But the evidence doesn’t entirely support this caution. For example, in a clinical
trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose
mean serum urate dropped below 2 mg/dL did not die in higher proportions than
patients with higher urate levels.
To better understand the risk of low urate, Baker and colleagues analyzed data
on 13,979 participants in the National Health and Nutrition Examination Survey
(NHANES) during 1999-2006. The dataset included whole-body dual energy x-
ray absorptiometry (DXA) body composition measures as well as urate levels.
The researchers argue this measurement reveals more about a person’s overall
health than body mass index (BMI), which doesn’t distinguish between mass
from fat and mass from muscle.
They defined low lean body mass, or sarcopenia, as an appendicular lean mass
index relative to fat mass index z-score of -1. And they defined low urate as less
than 2.5 mg/dL in women and less than 3.5 mg/dL in men.
They found that 29% of people with low urate had low lean body mass,
compared with 16% of people with normal urate levels. The difference was
statistically significant (P = .001).

They found an association between low urate and increased

mortality (hazard ratio [HR], 1.61; 95% CI, 1.14-2.28; P = .008).
But that association lost its statistical significance when the
researchers adjusted for body composition and weight loss (HR,
1.30; 95% CI, 0.92-1.85; P = .13).
Baker thinks the association between elevated mortality and low
urate can be explained by conditions such as cancer or lung
inflammation that might on one hand increase the risk of death
and on the other hand lower urate levels by lowering muscle
mass. “Low uric acid levels are observed in people who have lost
weight for unhealthy reasons, and that can explain relationships
with long-term outcomes,” he said.
Proportions of muscle and fat could not account for the risk of
mortality associated with high levels of urate, the researchers
found. Those participants with urate levels above 5.7 mg/dL had
a higher risk of death with higher levels of urate, and this
persisted even after statistical adjustment for body composition.
 Dr Mehdi Fini
The study sheds light on an important area of controversy, said
Mehdi Fini, MD, assistant professor of medicine at the University
of Colorado in Denver, who was not involved in the research.
But body composition does not entirely explain the relationship
between urate and mortality, he told Medscape Medical News.
Medications used to lower urate can cause side effects that
might increase mortality, he said.
Also, he said, it’s important to understand the role of
comorbidities. He cited evidence that low urate is associated with
renal, cardiovascular, and pulmonary conditions. Safe levels of
urate might differ depending on these factors. So rather than
applying the same target serum level to all patients, perhaps
researchers should investigate whether lowering urate by a
percentage of the patient’s current level is safer and more
effective, he suggested.
He agreed with an editorial that also appeared in Arthritis &
Rheumatology saying that there is no evidence for a benefit in
lowering urate much below 5 mg/dL. “No matter what, I think we
should just be careful,” Fini said.
Fini and Baker report no relevant financial relationships. Baker
acknowledged support from a VA Clinical Science Research &
Development Merit Award and a Rehabilitation R&D Merit
Award.
Arthritis Rheumatol. Published August 16, 2022. Abstract.