Association between ABCG2 transporter functionality and CKD progression: a retrospective cohort study in patients with CKD stage G3.

BACKGROUND: ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter for urate and uremic toxins, plays a critical role in extra-renal urate elimination. Its dysfunction leads to elevated serum urate (SU) levels and may promote renal tubular urate overload and uremic toxin accumulation, potentially contributing to chronic kidney disease (CKD) progression. METHODS: This retrospective cohort study included 317 patients with CKD stage G3, with 8,664 medical records (mean 6.74-year follow-up). ABCG2 function was estimated based on genotypes for p.Q126X and p.Q141K in the ABCG2 coding region: full function, mild dysfunction (approximately 75% function), and severe dysfunction (≤ 50% function). We performed generalized estimating equation analysis to assess the estimated glomerular filtration rate (eGFR) slope and Cox regression analysis to evaluate a > 30% decline in eGFR. The models were adjusted for age, sex, CKD etiology, renin-angiotensin system inhibitor use, proteinuria, and either CKD stage (G3a/G3b) or baseline eGFR, respectively. RESULTS: Owing to ongoing therapeutic interventions, no significant differences in SU levels were observed among ABCG2 functional groups at baseline. The eGFR slopes for fully functional, mildly dysfunctional, and severely dysfunctional ABCG2 were - 0.95 ± 0.12, - 0.94 ± 0.16, and - 1.37 ± 0.14 mL/min/1.73 m2/year, respectively. In the time-to-event analysis, severely dysfunctional ABCG2 was associated with a higher hazard ratio (HR) for > 30% eGFR decline during follow-up (HR, 2.72; 95% confidence interval, 1.11-6.66) compared to fully functional ABCG2. CONCLUSION: ABCG2 functionality is associated with renal prognosis in CKD and could be a useful marker for risk stratification in clinical settings.