Efficacy of febuxostat on hyperuricemia and estimated glomerular filtration rate in non-dialysis stage 3-4 chronic kidney disease patients and the assessment of cardiac function: 12-months interventional study

Yousuf Abdulkarim Waheed ^1,2 Fan Yang ¹ Jie Liu ³ Shifaa Almayahe ⁴ Karthick Kumaran Kumaran Selvam ¹ Disheng Wang ^1,2,5 Dong Sun ^1,2,5*

• ¹ The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ² Clinical Research Center For Kidney Disease Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ³ Second Affiliated Hospital, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ⁴ Medical college, University of Fallujah, Al Anbar Iraq, al anbar, Iraq
• ⁵ Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, Xuzhou, Jiangsu Province, China

Objectives: Febuxostat, an oral medication for treating hyperuricemia (HUA), is a nonpurine xanthine oxidase inhibitor that regulates the serum uric acid (SUA) metabolism in chronic kidney disease (CKD) patients. However, the drug's effectiveness in improving renal function in non-dialysis CKD stage 3-4 patients remains unclear. Furthermore, the cardiac function will be assessed. Method: We conducted a single-center, interventional randomized controlled, open-label study. A total of 316 non-dialysis stage 3-4 CKD patients, with SUA ≥6mg/dL in women and ≥7mg/dL in men were assigned to either febuxostat group (n=156) or control group (n=160), the endpoints were to evaluate the changes of kidney biomarkers from baseline to 12 months of treatment, and any changes in cardiac biomarkers and echocardiographs as a second endpoint. Results: The primary endpoint was a comparison between the two groups from baseline to 12 months of treatment, SUA was significantly decreased in subjects patients treated with febuxostat 40mg (6.85±0.41mg/dL at baseline and 5.27±0.70mg/dL at 12 months of treatment, P<0.001), this was associated with increased eGFR (34.48±8.42ml/min at baseline and 38.46±8.87ml/min at 12 months of treatment, P<0.001). There was a significant decrease in high-sensitivity troponin T in the febuxostat group (19.50±7.24ng/L at baseline and 16.98±7.32ng/L at 12 months of treatment, P<0.001), and N-terminal-pro brain natriuretic peptide (941.35±374.30pg/ml at baseline and 762.22±303.32 pg/ml at 12 months of treatment, P<0.001). These changes were also associated with increased left ventricular ejection fraction in the febuxostat group (50.47±3.95% baseline and 51.12±3.96% at the end of the study, P<0.001).Conclusion: For the interventional group, febuxostat was well tolerated and demonstrated a reduction in SUA associated with increased eGFR. This slowed down the progression of renal disease in non-dialysis CKD stage 3-4 patients and improved cardiac function.