Elevated Platelet Galectin-3 and Rho-Associated Protein Kinase Activity Are Associated with Hemodialysis Arteriovenous Shunt Dysfunction among Subjects with Diabetes Mellitus

الملخص EN

Introduction.

Hyperglycemia is a major factor in influencing the patency rate of arteriovenous shunts, potentially associated with the RhoA/Rho-associated protein kinase (ROCK) pathway.

Besides, galectin-3 mediates thrombotic mechanisms in venous thrombosis and peripheral artery disease.

We hypothesized that high ROCK activity and galectin-3 levels are associated with arteriovenous shunt dysfunction.

Methods.

We prospectively enrolled 38 patients diagnosed with arteriovenous shunt dysfunction.

29 patients received a complete follow-up and each provided two blood samples, which were collected at the first visit for occluded status of arteriovenous shunts and 1 month later for patent status.

A Western blot assay for a myosin phosphatase target subunit (MYPT) was performed to examine Rho-kinase activity.

A Western blot assay for platelet galectin-3 and enzyme-linked immunosorbent assay (ELISA) for circulating galectin-3 were completed.

Results.

Higher platelet MYPT ratios and galectin-3 levels were identified at occluded arteriovenous shunts (MYPT ratio: 0.5 [0.3–1.4] vs.

0.4 [0.3–0.6], p = 0.01; galectin-3: 1.2 [0.4–1.6] vs.

0.7 [0.1–1.2], p = 0.0004).

The plasma galectin-3 binding protein ELISA was also higher at occluded arteriovenous shunts (8.4 [6.0–9.7] μg/mL vs.

7.1 [4.5–9.1] μg/mL, p = 0.009).

Biomarker ratios (occluded/patent status) trended high in patients with poorly controlled diabetes (MYPT ratio: 1.7 [1.0–3.0] vs.

1.1 [0.7–1.3], p = 0.06; galectin-3: 1.6 [1.3–3.4] vs.

1.1 [0.8–1.9], p = 0.05).

Conclusion.

High platelet ROCK activity and galectin-3 levels are associated with increased risk in arteriovenous shunt dysfunction, especially in patients with poorly controlled diabetes.