Benefit of Urate-Lowering Therapy on Progression of Renal Disease

San Diego—For patients with hyperuricemia, urate-lowering therapy alone may not directly reduce the risk of kidney disease but may reduce other outcomes related to renal disease progression particularly in patients who achieve a serum acid of <6 mg/dL while on urate-lowering therapy.

These are the results of a retrospective study by investigators at Kaiser Permanente Downey Medical Center to examine the impact of urate-lowering therapy on renal function in a large cohort of patients with elevated uric acid.

The study included 16,168 patients identified through a database as having elevated serum uric acid levels (sUA) of >7 mg/dL between January 2002 and December 2010. All patients were >18 years of age; were not on dialysis; did not have chronic kidney disease, nonremission cancer, HIV, proteinuria, or kidney stones; and had not received a urate-lowering therapy (ie, allopurinol, probenecid, febuxostat) or organ transplant in the year prior to the study.

Prior to the study entry, all patients had at least 1 sUA and glomerular filtration rate (GFR) level during the 6-month study and at least 1 sUA and GFR during the follow-up period.

All patients were followed until they had an outcome event, disenrolled from the study, died, or the study ended in December 2011. Outcome events included >30% reduction in GFR, initiation of dialysis, or GFR <15 mL/min.

Patients were divided into 3 subgroups: (1) patients never receiving urate-lowering therapy (NT; n=11,182); (2) patients on urate-lowering therapy <80% of the time (<80%; n=3902); and (3) patients on urate-lowering therapy >80% of the time (>80%; n=1092). Overall, more of the patients in the >80% group were older, male, and had more comorbidities than patients in the <80% group or NT group. Compared to patients in the <80% group, patients in the >80% group received urate-lowering therapy earlier (16.9% vs 43.5%, respectively, initiated treatment within 2 weeks of study entry, and 41% and 94%, respectively, within 4 months).

Of the patients who received urate-lowering therapy, most (98.3%) received allopurinol. Overall, 1.2% of patients died during the study, with deaths represented equally among all 3 subgroups.

The study found a number of factors associated with outcomes events, including age, female gender, previous hospitalizations, higher sUA at baseline, rheumatoid arthritis, hypertension, diabetes, and congestive heart failure.

No association was found between time on therapy of >80% of the time and outcomes event (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.76-1.52; P=.68). The study did find, however, a significant 37% reduction in outcome events in patients who achieved an sUA of <6 mg/dL (HR, 0.63; 95% CI, 0.5-0.78; P<.0001).

Gerald Levy, MD, rheumatologist at Kaiser Permanente Downey Medical Center, Downey, California, the lead investigator of the study, presented the results study during the ACR/ARHP meeting. He emphasized that 1 major strength of the study is that it is based on real-world data and includes the largest number of patients with the most diverse population to date to look at the role of urate-lowering therapy on renal function in these patients.

Dr. Levy noted that future research is needed to examine whether renal function actually can improve with urate-lowering therapy.