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Abstract: TH-PO704

3-Carboxy-4-Methyl-5-Propyl-2-Furanpropionate (CMPF), a Protein-Bound Uremic Solute, Augments RBC Osmotic Fragility

Session Information

  • Anemia and Iron Metabolism
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Van Spitzenbergen, Beatriz Akemi Kondo, Pontificia Universidade Catolica do Parana, Curitiba, PR, Brazil
  • Ferreira Dias, Gabriela, Renal Research Institute, New York, New York, United States
  • Grobe, Nadja, Renal Research Institute, New York, New York, United States
  • Kotanko, Peter, Renal Research Institute, New York, New York, United States
  • Moreno-Amaral, Andrea Novais, Pontificia Universidade Catolica do Parana, Curitiba, PR, Brazil
Background

While contributing to renal anemia, shortened red blood cell (RBC) life span in end-stage kidney disease (ESKD) is poorly understood. Recently, the interaction between the protein-bound uremic solute 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) and the RBC Piezo1 mechanoreceptor has been hypothesized to shorten the RBC life span (Kotanko et al., FASEB J BioAdvances, 2022). In the present study, we evaluated the effect of CMPF on RBC osmotic resistance.

Methods

RBC were isolated from healthy subjects (n=6). CMPF (8 μM, 17 μM, 87 μM, 170 μM) dissolved in DMSO was added to cell suspensions. Buffer plus DMSO served as a negative control. From these suspensions, 10μL were added to increasing NaCl solutions, from 3 to 9 g/L. After centrifugation (1500 rpm; 10 min), Hg (540 nM) was measured in the supernatant. Data were fitted to a 4-parameter logistic regression curve. The osmotic fragility index (IC50) was defined as a NaCl concentration that exerted 50% hemolysis.

Results

CMPF increased osmotic fragility in a dose-dependent manner. IC50 at 17 μM, 87 μM, and 170 μM, respectively, exceeded controls (4.47±0.15 vs. 4.19±0.07, 4.66±0.10 vs. 4.12±0.11, 4.82±1.34 vs. 4.65±1.88), indicating increased hemolysis in the presence of CMPF (Table 1).

Conclusion

Our results indicate that CMPF increases RBC osmotic fragility in a dose-dependent manner. If and to what extent an interaction between CMPF and Piezo1 is the causal pathway warrants further studies.

Table 1 - Dose-dependent increase of RBC osmotic fragility induced by CMPF
 IC50 DMSO Neg Ctrl
(A)
IC50 CMPF
(B)
Mean of differences
(B - A)
p value
8 μM4.18±0.094.23±0.360.050.843
17 μM4.19±0.074.47±0.150.28*0.022
87 μM4.12±0.114.66±0.100.54**0.003
170 μM4.65±1.884.82±1.340.17*0.015

Data expressed as mean±SD.