Circulating Coagulation Regulator Levels After Lung Transplantation Are Associated with Acute Kidney Injury

Purpose

Acute kidney injury (AKI) is a common morbidity after lung transplantation, with postoperative rates up to 65%. Since microvascular coagulation contributes to AKI in preclinical models, we hypothesized that post-reperfusion circulating levels of the coagulation regulators plasminogen activator inhibitor-1 (PAI-1), protein C, and resistin, an inhibitor of protein C, would be associated with AKI.

Methods

The study population included 189 recipients enrolled from 7/2017-6/2019 in the 5-center Lung Transplant Outcomes Group Acute Kidney Injury (LTOG-AKI) prospective cohort study. We used Cuzick's nonparametric test of trend to examine the associations of plasma PAI-1, resistin, and protein C levels at 6 and 24 hours post-reperfusion with AKI severity (grouping stages 2-3) over the first 7 days post-transplant. We staged AKI using Kidney Disease Improving Global Outcomes creatinine criteria. We constructed ordinal logistic regression models of the association of each biomarker with AKI stage adjusting for preoperative biomarker levels, age, gender, chronic kidney disease, and transplant diagnosis.

Results

AKI stage 1 occurred in 45 (24%) and stage 2-3 in 50 (26%) patients. Hospital mortality was substantially higher in stage 2-3 AKI (18% vs 2% for both no AKI and stage 1 AKI, p=0.001). Plasma PAI-1 and resistin levels at 6h were associated with AKI stage (p<0.001, p=0.001, respectively), with similar findings at 24h (p<0.001, p=0.006, respectively). Protein C levels at 6h decreased with higher AKI stage (p=0.016). Six-hour PAI-1 and protein C remained associated with AKI stage in multivariable models, while the 6h resistin-AKI stage association was attenuated, particularly by adjustment for age and preoperative resistin levels (Figure 1).

Conclusion

Plasma levels of coagulation regulators at 6h post-lung transplant are associated with AKI stage and may offer insight into pathophysiologic mechanisms contributing to high AKI rates in this population.