Renal hyperfiltration with and without metabolic syndrome: differential implications for cardiovascular events, kidney failure, and mortality.

Background: Renal hyperfiltration (RHF) and metabolic syndrome (MetS) share common pathophysiology and are both associated with adverse clinical outcomes. However, their combined impact remains unclear. Methods: In total, 278,552 propensity score-matched individuals were enrolled in the Korean National Health Insurance Service database (2009-2011). Participants were divided into four groups based on RHF and MetS status, and cardiovascular (CV) events, end-stage kidney disease (ESKD) progression, and all-cause mortality were evaluated. Results: Compared to non-MetS with normal renal filtration (NRF), MetS with NRF was associated with a significant increase in the risk of CV events, which was further amplified when combined with RHF (adjusted HR = 1.44, 95% CI = 1.35-1.55, P for interaction = 0.047). Patients with RHF exhibited more pronounced increases in the HRs for CV events than those with NRF as the number of dysfunctional metabolic components increased (P for interaction = 0.019). The risk of ESKD progression was not increased in non-MetS with RHF; however, it was significantly higher in patients with MetS alone and highest in those with both MetS and RHF (adjusted HR = 3.23, 95% CI = 1.61-6.47). The risk of all-cause mortality was elevated in patients with RHF or MetS alone and highest in those with both RHF and MetS (adjusted HR = 1.41, 95% CI = 1.31-1.52). Conclusion: The clinical significance of RHF differs based on MetS status, with their coexistence posing the highest risk for CV events, ESKD progression, and all-cause mortality. A synergistic interaction between RHF and MetS was evident in the risk of CV events.