Evaluation of the Association between Age, Sex, and d-Amino Acid-Based Estimation of GFR

KEY POINTS: Blood d -serine and d -asparagine reflect GFR, reportedly with stable kinetics minimally influenced by age and tubular transport. d -Amino acid-based eGFR minimizes age and sex biases, a distinct advantage over conventional models. d -Amino acid-based eGFR holds broad clinical potential across all ages and populations. BACKGROUND: eGFR is challenging because of its dependence on age and body composition, especially in pediatric and elderly populations. Recently, d -serine and d -asparagine, rare amino acid enantiomers, have been identified as GFR biomarkers characterized by their ideal kidney clearance and minimal impacts of body size. We investigated the impact of age and sex on GFR estimation using these d -amino acids. METHODS: We analyzed data from a cross-sectional observational cohort: 366 adult Japanese living kidney transplant donors and recipients. Using a dataset of 244 patients, we developed GFR estimation formulae on the basis of blood levels of d -serine and d -asparagine using linear regression analyses and validated the formulas' performance in 122 patients. RESULTS: The d -amino acid - based equation was established as 60.4× d -Ser -0.450 × d -Asn -0.304 ×0.916 (if female), in which age did not significantly improve model performance and the impact of sex was minor. The performance of the established equations was equivalent to that of creatinine-based equations: bias (absolute difference), 9.1 (8.0-11.2); precision (interquartile range of bias), 11.1 (8.8-14.2); and accuracy (ratios of 30% different from measured GFR [P 30 ]), 0.82 (0.73-0.89). CONCLUSIONS: d -Amino acid-based estimation of GFR exhibits minimal empirical association with age and sex, offering a distinct advantage over models dependent on these demographic variables. This stability may support its broad clinical utility as a reliable diagnostic tool across all age groups and diverse populations.