Introduction

Febuxostat is a non-purine selective xanthine oxidase inhibitor. It effectively reduces serum uric acid (SUA) by inhibiting the enzymatic conversion of hypoxanthine and xanthine to uric acid.

Aim

To study outcomes of administering febuxostat to patients diagnosed with asymptomatic hyperuricemia in chronic kidney disease (CKD) (stages 3 and 4).

Patient Profile

• Patients with confirmed CKD in stages 3 and 4, who exhibited asymptomatic hyperuricemia and were undergoing outpatient or inpatient treatment
• Patients were aged 18 years or older with a serum uric acid level of 7 to 10.0 mg/dL and an estimated glomerular filtration rate (eGFR) range of 15–59 mL/min/1.73 m²

Method

• Quasi-experimental, single-patient blinded, placebo-controlled trial
• N=210
• Participants were randomly assigned into two groups

• Febuxostat group: Received a daily dose of 40 mg febuxostat.
• Placebo group: Received placebo tablets

• Assessments, including patient history, physical examinations, outcomes, and relevant tests, were conducted at baseline, as well as in the 3rd & 6th month.

Results

• The febuxostat treatment significantly reduced mean serum uric acid levels from 8.55 to 4.92 mg/dL over 6 months, whereas the placebo group experienced an increase from 8.10 to 8.99 mg/dL, with statistically significant differences between the groups at both 3 and 6 months (P < 0.001). (Figure 1)

Figure 1: Change in mean Serum uric acid levels at 3 & 6 months from baseline

• In the febuxostat group, the mean eGFR increased from baseline to 6 months from 25.28 to 27.01 ml/min/1.73 m², whereas in the placebo control group, it decreased from 26.81 to 23.32 ml/min/1.73 m²

Figure 2: Mean eGFR at baseline 3 months and 6 months between treatment groups

• Comparison of serum creatinine and eGFR from baseline to month 6 in the study groups
• After 6 months of treatment, the febuxostat group exhibited a reduction in serum creatinine levels and an increase in mean eGFR from baseline, but these changes were not statistically significant
• In contrast, the placebo group demonstrated a marked increase in serum creatinine levels and a decrease in eGFR after 6 months compared to baseline

Table : Changes in serum creatinine and eGFR from baseline from baseline to month 6 in the study groups

Study group	Variables (unit)	Mean (± SD) values		P value†
		At Baseline	At month 6
Febuxostat	Serum creatinine (mg/dL)	2.70 ± 0.63	2.45 ± 0.88	0.092
	eGFR (ml/min per 1.73 m­2)	25.28 ± 7.59	27.01 ± 8.29	0.164
Placebo	Serum creatinine (mg/dL)	2.54 ± 0.50	3.03 ± 1.5	0.003
	eGFR (ml/min per 1.73 m­2)	26.81 ± 7.31	23.32 ± 7.72	< 0.001

• In the febuxostat group, 40% patients had an eGFR decrease of 10% compared with 62.9% patients in the placebo group.

Figure 3: Percentage of patients experiencing a 10% reduction in eGFR at baseline

• After 6 months, febuxostat-treated patients exhibited lower systolic & diastolic blood pressure compared to the placebo group, with a statistically significant difference for systolic blood pressure (P = 0.05)
• A positive correlation was observed between the reduction of serum uric acid levels and the decrease in systolic blood pressure (P = 0.047) in study population , while the reduction in diastolic blood pressure was not statistically significant (P = 0.216)

Table :  Systolic BP and Diastolic BP between groups at baseline, 3 months, and 6 months period

Parameters (unit)	Time interval	Study groups	Mean ± SD	P value†
Systolic blood pressure (SBP)	Baseline	Febuxostat	137±7	0.680
		Placebo	138±8
	Month 3	Febuxostat	131±7	0.058
		Placebo	135±7
	Month 6	Febuxostat	130±8	0.023
		Placebo	134±7
Diastolic blood pressure (DBP)	Baseline	Febuxostat	86±8	0.250
		Placebo	84±8
	Month 3	Febuxostat	78±6	0.058
		Placebo	76±5
	Month 6	Febuxostat	76±6	0.025
		Placebo	80±7

Conclusion

Febuxostat effectively reduces serum uric acid levels and lowers systolic blood pressure in patients with hyperuricemia associated CKD, indicating its potential as a treatment option for this high-risk group. Although a trend towards eGFR stabilization was observed in the febuxostat group with stage 3 and 4 CKD, its renoprotective effects remain unclear.

Reference

Egypt. J. Intern. Med.2025; 37:58