medwireNews: The use of urate-lowering therapy (ULT) to reduce serum urate levels to below 6 mg/dL in people with gout and chronic kidney disease (CKD) does not increase the risks for severe or end-stage kidney disease, a study indicates.
Specifically, patients who reached the target serum urate level (TSUL) of less than 6 mg/dL within a year had a comparable 5-year risk for progressing to severe or end-stage kidney disease as those whose serum urate level remained above 6 mg/dL, with an adjusted nonsignificant hazard ratio (HR) of 0.89 and a nonsignificant HR of 0.67 for end-stage kidney disease alone.
Although there is no clear evidence that ULT worsens kidney function in patients who have gout and CKD, “some clinicians opt to withhold, reduce, or even discontinue ULT when a patient with gout experiences a decline in kidney function, complicating gout management,” write Jie Wei (Xiangya Hospital, Hunan, China) and colleagues in JAMA Internal Medicine. They say that their findings “suggest that lowering serum urate levels to less than 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals.”
The researchers used a target trial emulation approach based on data for 14,792 patients from the IQVIA Medical Research Database (IMRD), which contains electronic healthcare records collected from general practitioner clinical systems.
Eligible patients were 40–89 years old and had started taking ULT after being diagnosed with gout and CKD stage 3, defined as having an estimated glomerular filtration rate (eGFR) of 30–60 mL/min per 1.73 m² on at least two occasions more than 90 days apart within a year.
The patients were a mean of 73.1 years old and 62.3% were men. The vast majority, at 98.8%, were prescribed the ULT allopurinol while 1.2% received febuxostat.
The investigators found that 31.8% of the participants achieved TSUL within 1 year of starting treatment. They received ULT for a mean of 243.5 days while those who did not achieve TSUL were treated for a mean of 206.4 days.
Wei et al report that the adjusted 5-year risk for severe or end-stage kidney disease was comparable between those who did and did not achieve TSUL, at 10.32% versus 12.73%, giving a nonsignificant difference of 2.41 percentage points.
They note that the findings were consistent when they used the same approach but in patients who had gout and CKD stages 2 to 3, where CKD stage 2 was defined as having an eGFR between 60 and 90 mL/min per 1.73 m2 on at least two occasions more than 90 days apart within 1 year.
ULT may have benefits on kidney function by reducing glomerular hydrostatic pressure as a result of urate lowering or reducing endothelial dysfunction via an anti-inflammatory effect, Wei and colleagues say.
Thus, for patients with gout and CKD “[i]nitiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” they suggest.
However, the authors add that “[a]lthough ULT is generally well tolerated, it has been associated with rare but severe hypersensitivity reactions, such as allopurinol hypersensitivity syndrome. If future studies corroborate our findings, reassessing the risk-benefit ratio for using ULT in patients with gout and CKD may be warranted.”
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