Assessment of Urate-lowering therapies on lipid metabolism and kidney function in non-dialysis chronic kidney disease patients: 12 months multicenter cohort study

Yousuf Abdulkarim Waheed^1,2Huanhuan Yin³Jie Liu⁴Shifaa Almayahe⁵Maryam Bishdary⁶Karthick Kumaran Munisamy Selvam¹Syed Muhammad Farrukh⁷Shulin Li^1,2Disheng Wang^1,2,8Xinglei Zhou^4*Dong Sun^1,2,8*

• ¹The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ²Clinical Research Center For Kidney Disease Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ³Department of Nephrology, Fengxian People's Hospital, Xuzhou 221700, China, Xuzhou, China
• ⁴Second Affiliated Hospital, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ⁵Medical college, University of Fallujah, Al Anbar Iraq, al anbar, Iraq
• ⁶Central Michigan University, Mount Pleasant, Texas, United States
• ⁷Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ⁸Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, Xuzhou, Jiangsu Province, China

Background and objectives: Urate lowering therapies (ULTs) are primarily used to manage hyperuricemia (HUA), which refers to an increase in serum uric acid (SUA) levels. SUA is an important marker for assessing kidney function in patients complicated with chronic kidney disease (CKD). We aim to investigate the impact of ULTs on kidney function and lipid profiles in CKD patients, and further explore the sex-specific ULTs effects on lipid profiles. Method: We conducted a multicenter, prospective observational cohort study, enrolled n=200 patients aged between20 and 80 years old with stages 3/4 CKD. Patients were divided into two groups: the ULT group (n=94) who were receiving febuxostat or allopurinol, and the Non-ULT group (n=106) who were receiving their conventional CKD therapy, . Models adjusted for all collected confounders. All participants went through clinical assessment before and after treatment and were followed for 12 consecutive months. Results: LDL-c significantly decreased in the ULT group compared to the Non-ULT group after 12 months of observation (2.14 ± 0.32 vs. 2.42 ± 0.32 [95% CI: -0.36 to -0.18], P<0,001). Similarly, TC and TG were significantly decreased in the ULT group compared to the Non-ULT group after 12 months of observation (4.18 ± 0.44 vs. 4.47 ± 0.39 [95% CI: -0.40 to -0.16], P<0,001) for TC, and (2.43±0.62vs.2.63±0.58[95% CI: -0.37to-0.03], P<0,016) for TG. Moreover, HDL-c increased significantly in the ULT group compared to the Non-ULT group (1.41±0.13 vs. 1.23±0.15 [95% CI: 0.13to0.21], P<0.001). The sex-specific ULT on lipid profiles exhibited a greater reduction in LDL-c in males, and a more pronounced increase in HDL-c levels by (+0.23mmol/L[95% CI: 0.07to0.18], P<0.001). SUA significantly decreased in the ULT group compared to the Non-ULT group after 12 months of treatment. Similarly, eGFR slightly improved in the ULT group compared to the Non-ULT after 12 months of treatment. These results indicate the renoprotective effects of ULTs in CKD patients. Conclusion: In this cohort study of non-dialysis CKD patients, ULT use was associated with improved lipid profiles reduced LDL-c, TG, and TC; increased HDL-c, with greater HDL-c elevation and LDL-c reduction in males. ULTs exposure also correlated with attenuated CKD progression.