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Abstract: SA-PO559

Animal Models for Studying Protein-Bound Uremic Toxin Removal

Session Information

Category: Dialysis

  • 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Ahmed, Sabbir, Universiteit Utrecht, Utrecht, Utrecht, Netherlands
  • de Vries, Joost Christiaan, Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Lu, Jingyi, Universiteit Utrecht, Utrecht, Utrecht, Netherlands
  • Verrijn Stuart, Milan H., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Mihaila, Silvia M., Universiteit Utrecht, Utrecht, Utrecht, Netherlands
  • Vernooij, Robin W.m., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
  • Masereeuw, Rosalinde, Universiteit Utrecht, Utrecht, Utrecht, Netherlands
  • Gerritsen, Karin G., Universitair Medisch Centrum Utrecht, Utrecht, Utrecht, Netherlands
Background

Protein-bound uremic toxins (PBUTs) are linked with the progression of chronic kidney disease (CKD) and higher morbidity and mortality risks. Conventional dialysis does not effectively remove PBUTs due to their binding to plasma proteins. Therefore, novel approaches to improve PBUT clearance are being developed, but these require validation before clinical trials can be initiated. To gain more insight into suitable CKD animal models we conducted a semi-systemic review to document PBUT concentrations in various models and species.

Methods

The search yielded 1163 records which were included for abstract screening, of which 66 were included for data extraction (Figure 1). All data were extracted by one researcher, after which the data were independently validated by a second researcher. Two specific types of injury were distinguished and analyzed as subgroups for the effect on PBUT levels: nephron loss models (e.g. 5/6th nephrectomy) and tubular damage models (by administration of tubulotoxins, e.g. adenine).

Results

PBUT concentrations were reported in studies using rats (n=43), mice (n=16), dogs (n=3), cats (n=4), goats (n=1), and pigs (n=1). Most studies in rodents reported mean uremic concentrations of plasma indoxyl sulfate (IS) close to or in the range of human ESKD, with the highest concentrations in tubular injury models (121.7 μM (89.3 μM – 154.1 μM); mean (95% CI), n=15 rat studies). Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models (factor 11.2 versus 6.3 for nephron loss models), likely due to the fact that tubular secretory function was relatively more affected than glomerular filtration. The small number of studies and heterogeneity of the data reported precluded detailed analysis of large animal models or other PBUTs.

Conclusion

Tubular injury models in rats appear to be suitable models to mimic human ESKD for in vivo validation of innovative PBUT-lowering strategies.

Figure 1. Article selection process.

Funding

  • Government Support – Non-U.S.