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Kidney Week

Abstract: FR-OR79

A Cutting-Edge Multiphoton Microscopy-Based Approach to Test the Structure of the Peritoneal Membrane Reveals the Protective Effects of Glucose-Sparing Solution

Session Information

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • D'Apolito, Luciano, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy
  • Masola, Valentina, Universita degli Studi di Padova, Padova, Veneto, Italy
  • Shams, Abbas, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
  • D'Alessandro, Angelo, University of Colorado, Denver, Colorado, United States
  • Bonomini, Mario, Universita degli Studi Gabriele d'Annunzio Chieti Pescara, Chieti, Italy
  • Divino-Filho, Jose C., CLINTEC, Karolinska Institutet, Stockholm, Sweden
  • Arduini, Arduino, Iperboreal Pharma Srl, Pescara, Italy
  • Capasso, Giovambattista, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy
  • Trepiccione, Francesco, Biogem, Institute of Molecular Biology and Genetics, Ariano Irpino, Italy

Group or Team Name

  • Translational Nephrology Laboratory.
Background

Peritoneal dialysis (PD) is a renal replacement therapy that enables metabolic waste products and excess fluids to be eliminated through the peritoneal membrane. Exposure to conventional dialysates at high glucose content is considered critical for the pathogenesis of peritoneal fibrosis, angiogenesis, and epithelial-mesenchymal transition and leads to technique failure.
Pre-clinical research in this field suffers from limited in vivo models.
Here, we propose a method, based on multi-photon microscopy (MPM), that aims to study the physiology of the peritoneal membrane during dialysis exchange and to validate the effects of biocompatible dialysates in animal models.

Methods

By imaging the parietal peritoneum by MPM we are able to quantify blood flow, degree of fibrosis and vessels distribution. In vivo microscopy evaluation of peritoneal membrane was conducted in rats receiving for 15 days a daily i.p. injection of conventional glucose containing dialysate or a new glucose-sparing dialysate that keep iso-osmolality by substituting glucose with carnitine and xylitol (XyloCore).

Results

Treatment with XyloCore was associated with a lower thickness of the sub-mesothelial collagen deposition compared to glucose containing solution (p=0.013). In addition, the density of collagen fibers (p=0.012) and the vascular composition (p=0.006), as well as the number of branch points (p=0.0335), when compared to rats treated with a conventional PD solution was significantly lower. All these parameters were associated with a better functional performance at the PET test in the glucose-sparing group. Finally, metabolomic analysis of membrane extract and dialysate showed a marked difference in metabolic pathways.

Conclusion

Previous in vitro studies have shown that XyloCore is able to counteract the glucotoxic effects on the peritoneal membrane induced by conventional dialysates. Our in vivo approach confirms these findings and suggests that long-term protective effects may be achieved with XyloCore.