Measurement of glomerular filtration rate using endogenous D-serine clearance in living kidney transplant donors and recipients

Background Endogenous molecules that provide an unbiased and a precise evaluation of kidney function are still necessary. We explored the potential of clearance of D-serine, a rare enantiomer of serine and a biomarker of kidney function, as a measure of glomerular filtration rate (GFR). Methods This was a cross-sectional observational study of 200 living kidney transplant donors and recipients enrolled between July 2019 and December 2020 in a single Japanese center, for whom GFR was measured by clearance of inulin (C-in). Clearance of D-serine (C-DSer) was calculated based on blood and urine levels of D-serine, as measured by two-dimensional high-performance liquid chromatography. Analytical performance was assessed by calculating biases. Utilizing data from 129 participants, we developed equations for C-in based on C-DSer and C-cre using a linear regression model, and the performance was validated in 68 participants. Findings The means of C-in and C-DSer were 66.7 and 55.7 mL/min/1.73 m(2) of body surface area, respectively, in the entire cohort. C-DSer underestimated C-in with a proportional bias of 22.0% (95% confidence interval, 14.2-29.8%) and a constant bias of -1.24 (-5.78-3.31), whereas the proportional bias was minor to that of C-cre (34.6% [31.1-38.2%] and 2.47 (-1.18-6.13) for proportional and constant bias, respectively). Combination of C-DSer and C-cre measured C-in with an equation of 0.391 x C-DSer + 0.418 x C-cre + 3.852, which reduced the proportional bias (6.5% [-0.2-13.1%] and -4.30 [-8.87-0.28] for proportional and constant bias, respectively). In the validation dataset, this equation performed well with median absolute residual of 3.5 [2.3-4.8], and high ratio of agreement (ratios of 30% and 15% different from C-in [P-30 and P-15] of 98.5 [91.4-100] and 89.7 [80.0-95.2], respectively). Interpretation The smaller proportional bias compared to that of C-cre is an advantage of C-DSer as a measure of Cin. Combinational measurement of o-serine and creatinine, two endogenous molecules, has the potential to serve as a measure of GFR with precision and minor biases and can support important clinical decisions. Copyright (C) 2021 The Authors. Published by Elsevier Ltd.

Automated summary

This study explored the potential of D-serine clearance as a measure of GFR, showing that D-serine underestimated C-in levels but combining D-serine and creatinine measurements can reduce this bias, providing a more accurate method for GFR measurement.