Urinary Microcholesterol and Adverse Kidney Outcomes in CKD

Introduction: Urinary microcholesterol (U-mCHO) may reflect tubular or glomerular injury through impaired lipid handling; nonetheless, its prognostic value in chronic kidney disease (CKD) remains unclear. We examined whether U-mCHO is associated with adverse kidney outcomes. Methods: We conducted a cohort study of patients with CKD (baseline eGFR ≥ 15 ml/min per 1.73 m²), among whom baseline U-mCHO was measured between April 2022 and July 2022 and who were followed until December 2025. The primary outcome was major adverse kidney events (MAKE) with a 50% estimated glomerular filtration rate (eGFR) decline (MAKE50), defined as a composite of a ≥ 50% reduction in eGFR, initiation of kidney replacement therapy (KRT), or kidney-related death. Associations were evaluated using multivariable Cox models. Subgroup analyses focused on patients with low proteinuria (urinary protein-to-creatinine ratio [UPCR] < 0.5 g/g) using an alternative composite outcome (MAKE30) based on a 30% decline in eGFR. Results: A total of 1562 patients were included. The mean U-mCHO level was 3.0 ± 5.8 mg/g creatinine. Higher U-mCHO levels were associated with greater MAKE50 risk (adjusted hazard ratio [HR] for highest vs. lowest quartile: 7.30; 95% confidence interval [CI]: 2.74–19.49). This association was consistent when U-mCHO was modeled as a log-transformed continuous variable. The association remained consistent across subgroups and persisted in patients with low proteinuria (HR for MAKE30: 3.06; 95% CI: 1.37–6.85), with no interaction by proteinuria level (P = 0.89). Conclusion: U-mCHO is independently associated with MAKE50 in CKD. The association with MAKE30 was also observed in patients with low proteinuria, supporting U-mCHO as a potential noninvasive biomarker of kidney lipid injury.