Kidney Week

Abstract: SA-PO922

Theoretical Analysis of D-serine and D-asparagine as Biomarkers for Glomerular Filtration Rate

Session Information

• Pathology and Lab Medicine - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Kimura, Tomonori, Osaka Daigaku, Suita, Osaka, Japan

Tomonori Kimura, MD, PhD

• Tanaka, Ryo, Osaka Daigaku, Suita, Osaka, Japan

Ryo Tanaka, MD

• Higa, Yoko, Osaka Daigaku, Suita, Osaka, Japan

Yoko Higa

• Nakazawa, Shigeaki, Osaka Daigaku, Suita, Osaka, Japan

Shigeaki Nakazawa, MD

• Kakuta, Yoichi, Osaka Daigaku, Suita, Osaka, Japan

Yoichi Kakuta, MD, PhD

• Sakai, Shinsuke, Osaka Daigaku, Suita, Osaka, Japan

Shinsuke Sakai, MD

• Mizui, Masayuki, Osaka Daigaku, Suita, Osaka, Japan

Masayuki Mizui, MD, PhD

• Takahara, Shiro, Kansai Medical Clinic for Renal Transplantation, Toyonaka, Osaka, Japan

Shiro Takahara, MD, PhD

• Nonomura, Norio, Osaka Daigaku, Suita, Osaka, Japan

Norio Nonomura, MD, PhD

• Isaka, Yoshitaka, Osaka Daigaku, Suita, Osaka, Japan

Yoshitaka Isaka, MD, PhD

Background

As biomarkers that potentiate the precise measurement of glomerular filtration rate (GFR), two rare enantiomers of amino acids, D-serine and D-asparagine, are expected in use. This study aimed to analyze why the levels of these D-amino acids reflect GFR.

Methods

We utilized a cross-sectional observational study of 210 living kidney transplant donors and recipient, for whom GFR was measured using clearance of inulin. The levels of D-amino acids in blood and urine were measured using two-dimensional high performance liquid chromatography. The validity as GFR markers was assessed based on four criteria proposed previously: (i) free filtration at the glomeruli, (ii) constant clearance from plasma, (iii) no reabsorption at the tubules, (iv) no secretion at the tubules, (iv) endogenously present preferentially. We added two more criteria: (iv) endogenously present, preferentially, and (v) stable dynamics, regardless of GFR.

Results

D-Serine and D-asparagine are endogenously-present small molecules that are considered to pass through glomerular filtration barrier freely. Scatter plot analysis using clearance of inulin (C-in) as a reference showed that clearances of D-serine (C-dSer) and asparagine (C-dAsn) were well-correlated with C-in. These clearances are close to C-in with small proportional biases; the slope was 1.178 for C-dSer and 0.995 for C-dAsn, while the slope for C-cre was 0.674. Therefore, (i) D-serine and D-asparagine are subject to minor reabsorption and secretion in the tubules, or (ii) the reabsorption and secretion of these D-amino acids is balanced. Blant-Altman plot showed that the dissociations of C-dSer and C-dAsn from C-in were small and unaffected with the reduction of GFR.

Conclusion

D-Serine and D-asparagine are unaffected by tubular reabsorption and secretion after glomerular filtration. Additionally, tubular handling of D-serine and D-asparagine are unaffected by the reduced glomerular filtration. These features are the basis of D-serine and D-asparagine as biomarkers for GFR.