The Association Between Sublingual Microvascular Dysfunction and Plasminogen Activator Inhibitor-One Levels in Chronic Kidney Disease Patients: An Exploratory Study

Abstract

Objective

Explore potential associations between sublingual microcirculatory measures and plasma plasminogen activator inhibitor-one concentrations in patients attending the kidney transplant assessment clinic and healthy controls.

Methods

A single-center cohort study was performed by retrospectively recruiting 44 kidney transplant assessment clinic attendees and 15 nested non-renal failure controls who were selected from a larger pool (N = 44). The nested controls were frequency matched to the kidney transplant assessment clinic cohort by sex, ethnicity and diabetes. Sidestream dark field videomicroscopy (MicroScan, Microvision Medical, Amsterdam) of the sublingual microcirculation allowed quantification of five microcirculatory parameters in all patients: total vessel density, microvascular flow index, portion of perfused vessels, heterogeneity index and perfused vessel density. Plasma plasminogen activator inhibitor-one concentrations were determined using sandwich ELISA. Median (IQR) were reported for non-normally distributed data. Mann–Whitney-Wilcoxon tests were performed to compare the distribution of ranks between non-normally distributed groups (U-statistic) with p < 0.05 considered statistically significant. The Benjamini–Hochberg adjustment was applied to nominal p-values (q-value) to account for inflation of the false discovery rate across multiple exploratory analyses, with q < 0.05 considered statistically significant.

Results

Plasminogen activator inhibitor-one levels were significantly higher in controls than those attending the transplant clinic (18.0 (11.5), 10.2 (6.8) ng/mL; U = 158, p = 0.006). Among kidney transplant patients, nominal associations revealed PAI-1 was inversely correlated with hemodynamic parameters perfused vessel density (p = 0.04, r = −0.32) and microvascular flow index (p = 0.01, r = −0.38); neither survived the Benjamini–Hochberg adjustment (q = 0.24 and q = 0.12, respectively). No other correlations between PAI-1 and any of the sublingual microcirculatory measures survived the Benjamini–Hochberg adjustment in both cohorts.

Conclusion

PAI-1 is potentially associated with maladaptive hemodynamic changes in the sublingual microcirculation, implying its dysregulation may potentiate microvascular dysfunction. The results, however, must be interpreted with caution as no associations survived the Benjamini–Hochberg correction.