Endothelial biomarkers predict kidney and cardiovascular outcomes after acute kidney injury

Acute kidney injury (AKI) is common in hospitalized patients, and post-injury biological processes activated after the initial insult may determine recovery or sustained damage. Identifying these processes may offer opportunities for early intervention, and biomarkers can serve as valuable tools in this context. We hypothesized that endothelial biomarkers-reflecting endothelial dysfunction or damage-predict adverse clinical outcomes following AKI.

In a single-center cohort of 93 consecutive patients with in-hospital mild AKI, a panel of endothelial (sFlt-1, CD138, and sVCAM-1) and renal stress (IGFBP7, TIMP2, and their product [IGFBP7]*[TIMP2]) biomarkers was measured at diagnosis. Associations with in-hospital mortality, AKI duration ≥7 days, new-onset cardiovascular disease (CVD), and renal nonrecovery were examined using regression analyses.

Endothelial biomarkers were more closely associated with adverse outcomes than renal stress biomarkers in this cohort. After adjustment, each 100-unit increase in sFlt-1 was independently associated with higher odds of in-hospital death (OR 1.034 [1.007-1.062], P = 0.0144), new-onset CVD (OR 1.068 [1.029-1.108], P = 0.0005), and renal nonrecovery (OR 1.158 [1.045-1.284], P = 0.0052). Similarly, each 10-unit increase in CD138 was associated with increased odds of in-hospital mortality (OR 1.050 [1.014-1.088], P = 0.006) and new-onset CVD (OR 1.040 [1.004-1.077], P = 0.0304). Inclusion of endothelial biomarkers improved predictive performance for renal nonrecovery (AUC 0.86 vs. 0.75, P = 0.0163) and new-onset CVD (AUC 0.84 vs. 0.69, P = 0.0059).

Endothelial biomarkers, particularly sFlt-1 and CD138, provide insight into vascular health following AKI and independently predict clinical outcomes. Their integration into clinical models may improve risk stratification, supporting personalized post-AKI care strategies.