Lowering urates reduces kidney disease

Urate-Lowering Cuts Complications From Gout
Alice Goodman
Medscape
November 08, 2013

SAN DIEGO — Patients with gout who remain on urate-lowering therapy are less likely to develop kidney damage leading to chronic kidney disease than untreated patients, according to results from a large study.

There was an economic incentive to conduct this study, said lead investigator Gerald Levy, MD, a rheumatologist from Kaiser Permanente Medical Group in Downey, California. "Gout has increased dramatically over the past 20 years. With it, associated costs — including office visits, urgent care, emergency department visits, and hospitalizations — have gone up to about $1 billion per year."

Kaiser Permanente of Southern California covers 3.6 million people. "This is a big pile of patients," Dr. Levy told reporters attending a news conference here at the American College of Rheumatology (ACR) 2013 Annual Meeting.

"A number of studies show that people with renal disease can develop hyperuricemia, and some will also develop gout. We wanted to see if reversing uricemia would have an impact on renal disease," he explained.

Investigators identified 111,992 patients with serum uric acid levels above 7 mg/dL in the Kaiser Permanente database.

Of these, 16,186 had been tested for serum uric acid levels and glomerular filtration rates at least once in the 6 months prior to study entry and at least once during the follow-up period.

All of these patients were followed for 36 months from the first documented high serum uric acid level. Patients were grouped into categories: never treated with urate-lowering therapy (n = 11,192), on urate-lowering therapy less than 80% of the time (n = 3902), and on urate-lowering therapy more than 80% of the time (n = 1092).

Almost all of the patients receiving treatment were also on allopurinol (98.3%).

"Achieving serum uric acid below 6 mg/dL — as per ACR guidelines — was protective and associated with a 37% improvement in renal outcomes," Dr. Levy said. "These patients represent the real world."

Table. Effect of Urate-Lowering Therapy on Serum Uric Acid

Treatment Hazard Ratio 95% Confidence Interval P Value
Less than 80% of the time 1.27 1.05–1.55 .01
More than 80% of the time 1.08 0.76–1.52 .68
Serum uric acid at goal 0.63 0.50–0.78 <.0001

Patients taking urate-lowering therapy more than 80% of the time were older, sicker, and more likely to have a diagnosis of gout. They also initiated therapy earlier than patients in the other 2 groups.

Worse outcome was associated with age, being female, hypertension, diabetes, congestive heart failure, previous hospitalizations, higher serum uric acid level at entry, and rheumatoid arthritis. There was no difference in the number of deaths in the 3 groups.

A limitation of this study is that it was observational and retrospective, and some data points were missing, noted Dr. Levy.

"The next group of studies will assess whether we can actually improve renal function by lowering serum urate levels. We need to demonstrate this and see how long it takes to show improvement," he said. "We found changes in 36 months, and we believe these changes take place early. If we can prevent progression to chronic kidney disease and dialysis, this would have tremendous cost savings."

News conference moderator, Christie Bartels, MD, from the University of Wisconsin in Madison, noted that "the data for urate-lowering therapy in hyperuricemia are compelling, but we still need a prospective randomized controlled trial. The study findings are a plug for ACR guidelines for gout therapy, because many patients do not get to goal," she said.

Rheumatologists need to give patients a reason to stay on medications, Dr. Bartels added, and the fact that urate-lowering therapy might prevent a gout attack and preserve the kidneys could be that reason. " This is especially important in gout patients who present with kidney problems initially," she noted.

Dr. Levy and Dr. Bartels have disclosed no relevant financial relationships.

ACR 2013 Annual Meeting: Abstract 857. Presented October 27, 2013.