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. 2019 Dec;7(23):742.
doi: 10.21037/atm.2019.11.92.

Respiratory parameters and acute kidney injury in acute respiratory distress syndrome: a causal inference study

Tacyano Tavares Leite  1 , Cícero Abdon Malheiro Gomes  2 , Juan Miguel Cosquillo Valdivia  2 , Alexandre Braga Libório  2
Affiliations

Respiratory parameters and acute kidney injury in acute respiratory distress syndrome: a causal inference study

Tacyano Tavares Leite et al. Ann Transl Med. 2019 Dec.

Abstract

Background: Assess the respiratory-related parameters associated with subsequent severe acute kidney injury in mechanically ventilated patients with acute respiratory distress syndrome (ARDS).

Methods: Retrospective cohort, analyzing a large public database-Multiparameter Intelligent Monitoring in Intensive Care-III. Adult patients with at least 48 h of mechanical ventilation (MV), under volume controlled ventilation and an oxygenation index less than 300 mmHg were included.

Results: A total of 1,142 patients had complete data and were included in the final analyses. According to a causal directed acyclic graph (DAG) that included respiratory system compliance (Crs), tidal volume (Vt), driving pressure (ΔP), plateau pressure (PPlat), PEEP, PaO2 and PaCO2 as possible exposures related to severe AKI, only Crs and PEEP levels had significant causal association with severe acute kidney injury (AKI) (OR 0.90, 95% CI: 0.84-0.94 for each 5-mL/cmH2O reduction in Crs; OR, 1.05 95% CI: 1.03-1.10 for each 1-cmH2O increase of PEEP). Using mediation analysis, we examined whether any mechanical ventilation, blood gas or hemodynamic parameters could explain the effects of Csr on AKI. Only PEEP mediated the significant but small effect (less than 5%) of Csr on severe AKI. The effects of PEEP, in turn, were not mediated by any other evaluated parameter. Several sensitivity analyses with (I) need of renal replacement therapy (RRT) as an alternative outcome and (II) only patients with Vt <8 mL/kg, confirmed our main findings. In trying to validate our DAG assumptions, we confirmed that only ΔP was associated with mortality but not with severe AKI.

Conclusions: Crs and PEEP are the only respiratory-related variables with a direct causal association in severe AKI. No mechanical ventilator or blood gas parameter mediated the effects of Crs. Approaches reducing Vt and/or ΔP in ARDS can have limited effect on renal protection.

Keywords: Acute kidney injury (AKI); acute respiratory distress syndrome (ARDS); mechanical ventilation.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Directed acyclic graph with causality assumptions. Other clinical variables: age, gender, Elixhauser morbidity score, sepsis, SAPS I, vasoactive drugs, nephrotoxic drugs, baseline renal function, fluid balance before mechanical ventilation. Crs, respiratory system compliance; PEEP, positive end-expiratory pressure. Other clinical variables are represented in the graph as one unique box for simplicity but each clinical variable were included individually in the model.
Figure 2
Figure 2
Patient distribution in the MIMIC-III database and exclusion criteria. ARDS, acute respiratory distress syndrome; SCr, serum creatinine; Vt, tidal volume; PPlat, plateau pressure; PEEP, positive end-expiratory pressure.
Figure 3
Figure 3
Direct causal association between the Crs (A) and PEEP (B) with severe AKI after logistic regression, controlling for confounders.
Figure S1
Figure S1
Alternative pathway where ΔP is the exposure and Crs is treated as a mediator. The total effect of ΔP was adjusted for all non-respiratory related clinical variables and Vt. Crs, respiratory system compliance; ΔP, driving pressure; Vt, tidal volume per predicted body weight; AKI, acute kidney injury.
Figure S2
Figure S2
Alternative pathway where ΔP is the exposure and Crs is treated as a mediator. The total effect of ΔP was adjusted for all non-respiratory related clinical variables and Vt. Crs, respiratory system compliance; ΔP, driving pressure; Vt, tidal volume per predicted body weight; AKI, acute kidney injury.
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