Early Renal Trajectory in Sepsis-Associated Acute Kidney Injury: Role of Norepinephrine and Fluid Balance

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Abstract
Background: Sepsis-associated acute kidney injury (SA-AKI) affects 40–60% of septic patients and is associated with significant worsening of clinical outcomes. The impact of early haemodynamic strategies on renal function trajectory remains uncertain. Aim: To evaluate whether renal function trajectory in the first 96 h is influenced by norepinephrine exposure and cumulative fluid balance (CFB) and whether it affects outcomes in patients with SA-AKI. Methods: Prospective longitudinal observational study of 209 SA-AKI patients (1022 observations). Creatinine trajectory was analysed using linear mixed-effects models with time-dependent covariates (norepinephrine, CFB, diuretics), adjusted for baseline clinical characteristics. Lagged models assessed the association between prior exposures and subsequent renal function. Intra-patient before-after analyses and longitudinal models based on KDIGO classification were used as supporting analyses. Results: In linear models, norepinephrine was not associated with worsening of renal function. In lagged models, prior exposure was independently associated with lower subsequent creatinine values (β ≈ −0.105; p = 0.039). In the intra-patient analysis, norepinephrine initiation was associated with a creatinine reduction (−0.25 mg/dL; p < 0.001), with an effect attenuated by greater CFB. Norepinephrine exposure was also associated with a higher probability of KDIGO improvement between reassessments (OR 1.64; 95% CI 1.14–2.38; p = 0.008), maintained after adjustment for CFB and diuretics (OR 1.79; 95% CI 1.22–2.63; p = 0.003). In patients initiating norepinephrine, a reduction in KDIGO stage was observed (Δ −0.21; p = 0.049). Conclusions: Early use of norepinephrine is not associated with worsening of renal function and is associated, in temporal analyses, with improvement of renal trajectory, independently of fluid balance.

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