Kidney Week

Abstract: TH-PO1043

Elevated Plasma Free Sialic Acid Levels in Individuals with Reduced Glomerular Filtration Rates

Session Information

• Glomerular Diseases: Epidemiology, Mechanisms, Complications, Outcomes
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Fuentes, Federico, NIDDK, NIH, Bethesda, Maryland, United States

Federico Fuentes,

• Huizing, Marjan, National Institutes of Health/National Human Genome Research Institute, Bethesda, Maryland, United States

Marjan Huizing,

• Blake, Jodi, NIDDK, NIH, Bethesda, Maryland, United States

Jodi Blake,

• Gahl, William, National Institutes of Health/National Human Genome Research Institute, Bethesda, Maryland, United States

William Gahl,

• Carrillo, Nuria, National Institutes of Health/National Human Genome Research Institute, Bethesda, Maryland, United States

Nuria Carrillo,

• Kopp, Jeffrey B., NIDDK, NIH, Bethesda, Maryland, United States

Jeffrey B. Kopp,

Background

Sialic acid (SA) is a negatively charged, terminal monosaccharide present on glycoconjugates. They are important contributors to the polyanionic component of the glomerular filtration barrier, which regulates permeability selectivity. Free SA is filtered but not reabsorbed by the human kidney, in contrast to other sugars known to be reabsorbed by tubular cells. We determined plasma free SA levels of subjects with proteinuric diseases and diverse levels of estimated glomerular filtration rate (eGFR) to assess a correlation and emphasize this understudied feature of SA.

Methods

Free SA (Neu5Ac) was determined in plasma samples from 16 proteinuric subjects and 22 individuals with normal renal function with a validated LC-MSMS assay.

Results

There was a strong inverse relationship between eGFR and plasma SA levels (R² =0.70, p <0.0001). Plasma SA levels ranged between 114-206 ng/mL in subjects with normal eGFR (>90mL/min/1.73 m²). While in subjects with decreased eGFR (<30 mL/min/1.73 m²), plasma SA levels were at least three-fold higher (431-1260 ng/mL range).

Conclusion

It is important to emphasize the often-overlooked feature of renal handling of free SA. If increased plasma SA levels are encountered in subjects, compromised renal function/decreased eGFR should be considered. Of note is that pathologic hyposialylation of glomerular glycoconjugates, associated with podocyte effacement, has recently been implicated in human glomerulopathies. The relation between plasma free SA levels and glomerular hyposialylation remains to be investigated.

Funding

• NIDDK Support