ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

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.