Effect of topiroxostat-induced lowering serum uric acid on biomarkers of inflammation and tubular injury in chronic kidney disease patients with hyperuricemia: the planned secondary analysis of the target UA study

Background We conducted the planned secondary analysis using data from the Target UA study to assess the effect of lowering topiroxostat-induced serum uric acid (UA) on biomarkers of albumin-to-creatinine ratio (ACR), high-sensitivity C reactive protein (hsCRP), and neutrophil gelatinase-associated lipocalin (NGAL) levels. Methods Patients were divided into two groups based on serum UA levels at 52 weeks: serum UA < 5 mg/dL group (UA < 5 group) and serum UA ≥ 5 mg/dL group (UA ≥ 5 group). Serum UA, log ACR, xanthine oxidase activity, hsCRP, and NGAL were compared between the two groups. Multivariable linear regression analysis was used to evaluate the factors influencing log ACR. Results Data from 332 patients were analyzed. Mean serum UA was 4.27 mg/dL in the UA < 5 group and 6.25 mg/dL in the UA ≥ 5 group, with a difference of 1.98 mg/dL (p < 0.0001). The serum UA at 52 weeks did not significantly affect the log ACR (P = 0.0554). Among 77 patients with baseline hsCRP > 0.2 mg/dL, the proportion of those with hsCRP < 0.2 mg/dL at 52 weeks was higher in the UA < 5 group than that in the UA ≥ 5 group (75.0% vs. 47.5%, p = 0.0453). Among 33 patients with NGAL > 30.5 ng/mL at baseline, the proportion of those with NGAL ≤ 30.5 ng/mL at 52 weeks was higher in the UA < 5 group than that in the UA ≥ 5 group (72.7% vs. 31.8%, p = 0.0245). Conclusion Although the topiroxostat-induced impact on ACR was limited in this study, the results suggest that UA-lowering therapy may offer benefits in reducing inflammation and tubular damage, as indicated by hsCRP and NGAL levels (UMIN000026741 and jRCTs051180146).