Structural equation modelling exploration of the key pathophysiological processes involved in cardiac surgery-related acute kidney injury in infants

Abstract

Background: Uncertainties about the pathophysiological processes resulting in cardiac surgery-related acute kidney injury (AKI) in infants concern the relative impact of the most prominent risk factors, the clinical relevance of changes in glomerular filtration rate vs tubular injury, and the usefulness of available diagnostic tools. Structural equation modelling could allow for the assessment of these complex relationships.

Methods: A structural model was specified using data from a prospective observational cohort of 200 patients <1 year of age undergoing cardiopulmonary bypass surgery. It included four latent variables: AKI, modelled as a construct of perioperative creatinine variation, of oliguria and of urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations; the cardiopulmonary bypass characteristics; the occurrence of a post-operative low cardiac output syndrome and the post-operative outcome.

Results: The model showed a good fit, and all path coefficients were statistically significant. The bypass was the most prominent risk factor, with a path coefficient of 0.820 (95 % CI 0.527-0.979), translating to a 67.2 % explanation for the risk of AKI. A strong relationships was found between AKI and early uNGAL excretion, and between AKI and the post-operative outcome, with path coefficients of 0.611 (95 % CI 0.347-0.777) and 0.741 (95 % CI 0.610-0.988), respectively. The path coefficient between AKI and a >50 % increase in serum creatinine was smaller, with a path coefficient of 0.443 (95 % CI 0.273-0.596), and was intermediate for oliguria, defined as urine output <0.5 ml kg(-1) h(-1), with a path coefficient of 0.495 (95 % CI 0.250-0.864). A path coefficient of -0.229 (95 % CI -0.319 to 0.060) suggested that the risk of AKI during the first year of life did not increase with younger age at surgery.

Conclusions: These findings suggest that cardiac surgery-related AKI in infants is a translation of tubular injury, predominately driven by the cardiopulmonary bypass, and linked to early uNGAL excretion and to post-operative outcome.

Trial registration: ClinicalTrials.gov identifier NCT01219998 . Registered 11 October 2010.

Keywords: Acute kidney injury; Cardiopulmonary bypass; Paediatric cardiac surgery.

Fig. 1

Variation as a function of time for the parameters included in the structural equation model. Duration of monitoring varied between 12 and 48 h after surgery. NGAL neutrophil gelatinase-associated lipocalin, ΔsCr variation of serum creatinine relative to baseline

Fig. 2

Diagram of the structural equation model. The path coefficients shown above each single-headed arrow are standardized partial regression coefficients, indicating to what extent a change of the variable at the tail of the arrow is transmitted to the variable at the head of the arrow (with all other variables indicated in the diagram held constant). The coefficients shown above double-headed arrows are covariance coefficients. Residual arrows were omitted. All path coefficients were statistically significant (p < 0.001). *Modelled using the AUCs, accounting for the magnitude and the duration of the parameter variation. AKI acute kidney injury, CPB cardiopulmonary bypass, ICU intensive care unit, LCOS low cardiac output syndrome, ΔsCr variation of serum creatinine relative to baseline, uNGAL urine neutrophil gelatinase-associated lipocalin