Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia

1. Moh’d Sharshir, MD
Nephrology Fellow

2. Background:
o Hyperuricemia has been associated with adverse outcomes in CKD.
Hyperuricemia has been linked to macrovascular heart disease in
diabetic CKD.

3. Background:
o
o High uric acid levels have been reported to be associated with
increased rates of decline in glomerular filtration rate (GFR) in cross-
sectional studies.

4. Background:
o Febuxostat is a xanthine oxidase inhibitor shown to be efficacious in
hyperuricemia and gout.
o It does not require dose modification in patients with kidney failure.

5. Aim of the study:
o To determine the efficacy of febuxostat compared to placebo for
slowing eGFR decline in patients with CKD stages 3 and 4 (eGFR, 15-60
mL/min/1.73 m2) and asymptomatic hyperuricemia (uric acid > 7
mg/dL).
o To compare the incidence of adverse cardiovascular events (myocardial
infarction, cerebrovascular events, and heart failure), death, and
hospitalization rates between the 2 groups.

6. Study Design:
o This was a single-center, double-blind, randomized, parallel-group,
placebo-controlled study.
o Setting & Participants: Eligible participants were adults from Eastern
India aged 18 to 65 years with CKD stages 3 and 4, with asymptomatic
hyperuricemia.

7. Study Design:
o Intervention: The intervention group received febuxostat, 40 mg, once
daily for 6 months, while the placebo group received placebo; both
groups were followed up for 6 months.
o Patients were recruited from February 2012 through January 2013 and
follow-up of the last patient ended in July 2013.

8. Outcomes:
 The primary outcome : was the proportion of patients showing a
>10% decline in estimated glomerular filtration rate (eGFR) from
baseline in the febuxostat and placebo groups.
 Secondary outcomes : included changes in eGFRs in the 2 groups
from baseline and at the end of the study period.

9. RESULTS

15. Adverse events:
o Adverse events that could be directly attributed to the drug were very
few; only 2 patients had mild diarrhea, both in the febuxostat group,
while none in the placebo group had adverse reactions. Neither of
these 2 patients required discontinuation of therapy.

16. Conclusions:
Febuxostat slowed the decline in eGFR in CKD
stages 3 and 4 compared to placebo.