WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
Dr. Ana Beatriz Vargas-Santos
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
Dr. Gerald D. Levy
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.