A prealbumin-containing TyG-FPR-AISI composite for clinically significant early sepsis-associated acute kidney injury: a single-center derivation cohort study with internal validation.

Background: Sepsis-associated acute kidney injury (SA-AKI) is heterogeneous in severity and biological drivers. Early identification of clinically significant SA-AKI remains challenging because conventional severity markers and kidney-function criteria do not fully capture metabolic stress, inflammatory-coagulopathy burden, and host-reserve/catabolic-inflammatory status. We evaluated whether a routinely available prealbumin-containing TyG-FPR-AISI composite provides incremental risk-stratification value for clinically significant early SA-AKI. Methods: This single-center retrospective derivation cohort included 359 septic ICU patients between January 2018 and December 2024. The primary endpoint was clinically significant early SA-AKI within 48 h after T0, defined as serum creatinine-defined KDIGO stage 2-3 AKI or renal-indication RRT/CRRT. Patients without the primary endpoint and with < 48 h of ICU observation were excluded from the main analysis, yielding 325 patients. TyG, fibrinogen-to-prealbumin ratio (FPR), and aggregate index of systemic inflammation (AISI) were measured within 0-24 h after T0. An equal-weight composite was calculated as the mean of standardized TyG, FPR, and AISI. Logistic regression, ROC analysis, fivefold cross-validation, calibration assessment, Brier score, decision curve analysis, and sensitivity analyses were performed. Results: Clinically significant early SA-AKI occurred in 69 of 325 patients (21.2%). FPR was independently associated with the primary endpoint (adjusted OR 1.36 per 1-SD increase, 95% CI 1.05-1.76), whereas TyG and AISI showed directionally positive but weaker associations. The equal-weight composite was independently associated with clinically significant early SA-AKI (adjusted OR 1.58 per 1-SD increase, 95% CI 1.20-2.07). Model 0 plus the composite improved apparent AUC from 0.671 to 0.706 and fivefold cross-validated AUC from 0.608 to 0.653, with a lower Brier score (0.147 vs. 0.155). Higher composite tertiles were associated with more severe KDIGO categories and persistent AKI at day 7. Sensitivity analyses supported the composite association for any-stage creatinine-defined SA-AKI, while associations were attenuated when urine-output criteria were incorporated. Conclusions: The prealbumin-containing TyG-FPR-AISI composite was associated with clinically significant early SA-AKI and short-term AKI persistence, but its incremental performance beyond a clinical baseline model was modest. These findings support its exploratory role as a routinely available nutrition-relevant host-response risk-enrichment signal rather than a stand-alone prediction tool; external validation and recalibration are required before clinical application.