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.

Table 1: Cox Proportional Hazard Model for Risk Factors