Impact of Urate-Lowering Therapy on Kidney Disease in People with Hyperuricemia

Treating to the 2012 American College of Rheumatology Guidelines for Management of Gout

Released: 18-Oct-2013 12:00 PM EDT
Embargo expired: 26-Oct-2013 4:30 PM EDT
Source Newsroom: American College of Rheumatology (ACR)
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Citations American College of Rheumatology Annual Meeting

Newswise — SAN DIEGO – Urate-lowering therapy alone may not directly reduce the risk of kidney disease in those with hyperuricemia. However, according to a study presented this week at the American College of Rheumatology Annual Meeting in San Diego, working to lower serum uric acid based on the 2012 American College of Rheumatology Guidelines for Management of Gout has a positive effect.

When the amount of uric acid in the blood reaches an unusually high level, it is called hyperuricemia. It has been established in previous studies that there is a connection between hyperuricemia and chronic kidney disease. There have been several small studies on the impact of urate-lowering treatments on the progression of kidney disease, and Kaiser Permanente Southern California researchers recently conducted a large study that evaluated patients with hyperuricemia and the impact of urate-lowering treatments on kidney function.

“This is the largest study with the most diverse population to examine the role of urate lowering therapy (ULT) on renal function in patients with elevated uric acid,” says Gerald Levy, MD; rheumatologist, Kaiser Permanente Downey Medical Center; and lead author in the study.

Using database information from January 1, 2002 through December 31, 2010, Dr. Levy’s team identified 111,992 patients with serum uric acid levels of at least 7mg/dL. To be included in the study, the patients needed to be at least 18 years old, not on dialysis, and without chronic kidney disease, HIV, non-remission cancer, proteinuria or kidney stones. Additionally, the patients must not have received an organ transplant, and they must not have taken ULT (i.e., allopurinol, probenecid and febuxostat) in the year prior to joining the study. A total of 16,186 patients were ultimately included in the study.

Patients had at least one serum uric acid and glomerular filtration rate level within six months prior to study entry and at least one of each in the follow up period. Outcome events were defined as: 30 percent or greater reduction in glomerular filtration rate, dialysis, or glomerular filtration rate falling to less than 15 ml/min. Patients were followed until an outcome event, death or withdrawl from the study.

The patients were divided into three groups. The first group (11,192 patients) was never treated with ULT; the second (3,902 patients) was on ULT less than 80 percent of the time; the third (1,092 patients) was on ULT 80 percent or more of the time. The majority of patients who took ULT during the course of the study were taking allopurinol (98.3 percent), and no one group experienced a higher percentage of deaths during the study than the other groups.

Dr. Levy’s team noted that the group receiving urate-lowering therapy 80 percent or more of the time of the study tended to be older men with more co-existing diseases when compared to the other two groups. They also began the therapy earlier. For example, 43.5 percent in the over 80 percent group started the therapy within two weeks of the study compared to 16.9 percent in the less than 80 percent group and 94 percent started the therapy within six months compared to 41 percent in the less than 80 percent group.

Additionally, the team determined that age, female gender, having high blood pressure, diabetes or congestive heart failure, previous hospitalizations, having higher serum uric acid levels at the beginning of the study, and having rheumatoid arthritis were all associated with the three outcome events in the study.

Patients on urate-lowering therapy for 80 percent or more of the time of the study and achieved a serum uric acid level of 6mg/dL had a 37 percent reduction in outcome events. A serum uric acid level of less than 6 mg/dl level is the treatment goal in the 2012 American College of Rheumatology Guidelines for Management of Gout. Thus researchers believe that treating to the ACR’s guidelines is an effective way of preventing and controlling kidney disease in people with hyperuricemia.

“Patients who take urate lowering therapy and achieve a serum uric acid of less than 6 milligrams per deciliter, consistent with the new ACR guidelines, demonstrate a 37 percent reduction in progression of renal disease,” explains Dr. Levy. “The takeaway message here is that we can help support patients with hyperuricemia, by preventing and controlling kidney disease and maintaining treatment goals. Using our electronic health records and integrated system already in place, we can help keep patients healthy for longer and deliver continuity of care.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official hashtag: #ACR13.

Editor’s Notes: Dr. Levy will present this research during the ACR Annual Meeting at the San Diego Convention Center at 4:45 PM on Sunday, October 27 in Hilton – Sapphire A. Dr. Levy will be available for media questions and briefing at 1:30 PM on Sunday, October 27 in the on-site press conference room, 27 AB.

Abstract Number: 857

Impact of Urate Lowering Therapy On Renal Disease Progression in Patients With Hyperuricemia

Gerald D. Levy1, T. Craig Cheetham2, Nazia Rashid3 and Fang Niu2, 1Southern California Permanente Medical Group, Downey, CA, 2Kaiser Permanente, Downey, CA, 3Kaiser Permanente Southern California, Downey, CA

Background/Purpose: The relationship between elevated serum Uric Acid [sUA] and progression of chronic kidney disease is well established.1-3 There are a several small studies on the impact of Urate Lowering Therapy (ULT) on renal progression or ESRD.4-6 This large study evaluated patients with hyperuricemia and the impact of ULT on renal function.

Methods: This retrospective, database study identified 111,992 patients with a serum uric acid level (sUA) of ≥ 7mg/dl [Index Date (ID)] from January 1, 2002 to December 31, 2010. Patients with at least 12 months of Health Plan membership including drug benefit prior to ID were studied. All patients had at least one sUA and Glomerular Filtration Rate (GFR) level within the 6 months period prior to the ID and at least one sUA and GFR in the follow up period following the ID (follow up period). A ≥ 30% reduction in GFR, initiation of dialysis or a GFR ≤ 15 ml/min were defined as Outcome Events. All subjects were ULT naïve to allopurinol, probenecid and febuxostat in the 12 months before the ID. At ID, subjects were ≥18 years of age, without chronic kidney disease (CKD) 4 or 5, on dialysis, HIV, non-remission cancer, proteinuria, nephrolithiasis, or organ transplantation. Patients who met inclusion criteria were followed until they had an Outcome Event, disenrolled, died, the end of the follow up period or the conclusion of the study, 12/31/2011.. The cohort was subdivided into three groups: never treated (NT), ULT time on therapy of <80% (<80%) and time on therapy of ≥80% (≥80%). Cox proportional hazards regression model was used to determine factors associated with renal function decline.

Results: A total of 16,186 patients met inclusion criteria with 11,192 NT patients, 3,902 with <80% and 1,092 with ≥80%. The ≥80% group tended to be older, male with more co-morbidities compared to NT or <80% groups. The ≥80% group received ULT earlier than <80% group with 43.5% compared to 16.9% starting within 2 weeks of ID and 94% compared to 41% starting within 4 months. Allopurinol accounted for 98.3% of ULT and deaths were equally represented amongst the groups at 1.2%. Factors associated with outcome events were age, female gender, hypertension, diabetes, congestive heart failure, previous hospitalizations, higher sUA at baseline and rheumatoid arthritis. Time on therapy of ≥80% was not associated with outcome events 1.07 (0.76-1.52, p=0.68) however those patients with a sUA <6mg/dL had a significant 37% reduction in events p=<0.0001 HR 0.63 (0.5-0.78). See Table 1.

Conclusion: Serum Uric Acid is an independent risk factor for progressive renal function decline. Time on ULT was not associated with a reduction in renal disease progression, but in patients who achieved the ACR goal of sUA <6mg/dL7 there was a 37% reduction in outcome events.


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