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Kidney Week

Abstract: TH-PO734

Bedside Assessment of the Microcirculation in Patients with Fabry Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Bertram, Anna, Hannover Medical School, Hannover, Germany
  • Peede, Lisa Katharina, Hannover Medical School, Hannover, Germany
  • Goldenberg, Natalia, Medizinische Hochschule Hannover, Hannover, Germany
  • Kaufeld, Jessica Katharina, Medical School of Hannover, Hannover, Germany
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
Background

Fabry disease is a hereditary lysosomal storage disease with a loss of α-galaktosidase A activity, in which accumulation of glycosphingolipids leads to cellular damage in endothelial cells and other cell types. The endothelial surface layer (ESL) with the glycocalyx is important for endothelial cell function. We, therefore, assessed the ESL as well as circulating components of the ESL in Fabry patients. Visualization of the microcirculation can lead to a better understanding of its contribution to the pathophysiological changes in Fabry disease.

Methods

29 patients with Fabry disease and 33 healthy age- and gender-matched controls were analysed by intravital microscopy with the GlycoCheck™ technology (Micro Vascular Health Solutions) to measure ESL thickness (perfused boundary region), red blood cell filling velocity, and microvascular density. Circulating ESL components (syndecan-4, thrombomodulin), cytokines (MCP-1), and regulatory molecules (ADAM-17, VEGF-R1) were measured in plasma using ELISA. Patients were clinically characterized by organ involvement (heart, kidney, brain).

Results

Perfused boundary region was significantly decreased in patients with Fabry disease (1.96 ± 0.28, vs. 2.36 ± 0.27, p = 0.001). Circulating markers of the ESL were not different between groups. Microvascular density was significantly lower in Fabry patients compared to controls (median 284.50 vs. 580.83 µm/mm2, p = 0.001). The alterations in microcirculation were independent of the degree of organ involvement. MCP-1 concentration was significantly increased in Fabry patients (346.19 ± 91.82 pg/ml vs. 288.13 ± 95.22 pg/ml, p = 0.018) which was pronounced in patients with cardiac involvement.

Conclusion

Our data suggest an increase in ESL density, and no change in glycocalyx breakdown in patients with Fabry disease. In addition, a rarefication of microvessels was observed. Our findings suggest pathophysiological changes in the microvascular structure of patients with Fabry disease. The enhanced inflammation is not directly related to the microvascular changes.