Does kidney function in experimental porcine sepsis fulfill the RIFLE criteria for acute kidney injury? A systematic...

Sepsis is a leading cause of acute kidney injury (AKI) in patients treated in intensive care units. Due to close resemblance between porcine and human anatomy and physiology, porcine models are increasingly utilized in investigations of pathophysiological mechanisms behind sepsis associated AKI.

The aim of this review was to assess the renal function in untreated porcine models of sepsis using the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria at the group level.

The review was pre-registered in the Open Science Framework, DOI 10.17605/OSF.IO/FC29M. A systematic literature search was performed to identify porcine sepsis models which fulfilled the RIFLE criteria in the absence of active treatment. Three databases (Medline, Embase, and Web of Science) were systematically searched from 1946 until April 29^th, 2025. In vivo studies aiming to induce sepsis or sepsis like conditions were included if the RIFLE criteria could be assessed at the group level in at least one study group. A meta-analysis was performed to study the relation between sepsis induction method and the likelihood of fulfilling the RIFLE criteria.

1270 records were retrieved via databases and registers. Additional 309 records were identified from citation searching. 64 studies were included in the systematic review. 30 of 64 (47%) studies fulfilled one of the RIFLE criteria. 16, 9 and 5 studies fulfilled the RIFLE Risk, Injury and Failure criteria, respectively. 28 out of 64 studies (44%) reported renal dysfunction, but only two studies defined AKI using a diagnostic criterion. Exogenous markers of glomerular filtration rate (GFR) were applied in three studies. Fulfilment of the RIFLE criteria was associated with GFR being reported (p = 0.007), while the meta-analysis found no difference in the rate of AKI between different sepsis induction methods (Q_between = 2.49, p = 0.48).

AKI at the group level was identified in 47% of the included studies. Exploratory meta-analyses did not identify any statistically robust differences in RIFLE fulfilment between sepsis induction methods, but methodological heterogeneity significantly limited the interpretability of the meta-analysis. Measurement of GFR was associated with a higher likelihood of RIFLE fulfilment, while the use of precise markers appeared limited.