CKD, Uric Acid, and Heart Disease: What's the Link?

Chronic kidney disease (CKD) patients with gout saw poorer heart health and may benefit from preemptive treatment, a researcher suggested.

Among more than 500 CKD patients from a single kidney center, rates of cardiovascular disease were nearly double among those who also had comorbid hyperuricemia or gout compared with the overall practice patient population (32.3% vs 17.6%, P<0.00001), reported Raj Alappan, MD, of Renal Associates in Columbus, Georgia.

Cardiovascular disease was slightly more common in patients with gout versus those with asymptomatic hyperuricemia (18.4% vs 13.9%), although this difference didn't reach statistical significance, according to the findings presented at the National Kidney Foundation's virtual Spring Clinical Meeting.

A total of 257 patients in the retrospective analysis had hyperuricemia (defined as a uric acid level of 6.5 mg/dL or higher at any time while at the practice) and another 256 patients had symptomatic hyperuricemia or gout (defined as having "gouty arthritis" or receiving gout treatment). Uric acid levels were taken during the patients' first visit to the renal practice and CKD staging was defined according to estimated glomerular filtration rate (eGFR).

Hypertension was another clinical factor tied to uric acid levels. Patients with gout -- but not asymptomatic hyperuricemia -- had significantly lower levels of uric acid if they were free of hypertension (6.73 mg/dL vs 8.12 mg/dL with hypertension).

When broken down by CKD stage, average uric acid levels increased with more advanced stages of CKD. Similar trends were seen in those with hyperuricemia and gout as well, with mean uric acid level steadily increasing with more advance CKD stages.

Again, this same trend was seen in the subgroup of patients with heart disease, with the largest gap seen among patients with stage 3 CKD (mean uric acid 8.61 vs 8.02 mg/dL in the overall population).

"Several findings were surprising," Alappan told MedPage Today by email. "We did not expect to see such strong, positive, linear correlations between uric acid level and CKD-stage in overall, hyperuricemic, gout, and cardiovascular disease populations," he explained, putting special emphasis on the findings within the cardiovascular disease population.

He also expressed surprise at finding demographic differences in uric acid and cardiovascular disease occurrence.

Race was one strong predictor of this, as white patients with cardiovascular disease had significantly higher mean uric acid levels versus black patients with cardiovascular disease (8.40 vs 7.76 mg/dL, P=0.03). But in the general kidney patient population with comorbid cardiovascular disease, mean uric acid levels didn't differ by race.

Age and sex were other mediating factors tied to uric acid levels in patients with kidney disease. Among women, uric acid levels jumped to an average of 8.12 mg/dL by the age of 65 -- significantly higher than those under 65, who had average levels of 7.19 mg/dL. On the other hand, no significant differences were seen for rates of cardiovascular disease between women with CKD over or under age 65.

Men saw opposite trends, however. By the age of 65, rates of cardiovascular disease jumped significantly -- 36% in those 65 years or older versus 23% in men under 65. But age didn't seem to play a role in average uric acid levels in men.

Based on the links between kidney disease, uric acid, and cardiovascular disease, Alappan suggested proactive prevention measures be taken for certain patients.

"With no current consensus on treatment of asymptomatic hyperuricemia, we propose preemptive treatment of all hyperuricemic patients -- or at minimum those symptomatic (gout) with uric acid level ≥10 mg/dL -- to mitigate potential development of gout, cardiovascular disease, and hypertension," he said, adding that future studies are warranted to assess the long-term benefits of treating these patients with hyperuricemia.

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