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

Autor: Kawamura M; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Hesaka A; KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.; Reverse Translational Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan., Taniguchi A; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Nakazawa S; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Abe T; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Hirata M; Laboratory of Rare Disease Resource library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN)., Sakate R; Laboratory of Rare Disease Resource library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN)., Horio M; Department of Nephrology, Kansai Medical Hospital, Osaka, Japan., Takahara S; Department of Renal Transplantation, Kansai Medical Hospital, Osaka, Japan., Nonomura N; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Isaka Y; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan., Imamura R; Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Kimura T; KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.; Reverse Translational Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.; Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.; Laboratory of Rare Disease Resource library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN).
Jazyk: angličtina
Zdroj: EClinicalMedicine [EClinicalMedicine] 2021 Dec 05; Vol. 43, pp. 101223. Date of Electronic Publication: 2021 Dec 05 (Print Publication: 2022).
DOI: 10.1016/j.eclinm.2021.101223
Abstrakt: 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 × C-dSer + 0.418 × 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 C-in. Combinational measurement of d-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.
Funding: Japan Society for the Promotion of Science (JSPS, grant number 17H04188), Japan Agency of Medical Research and Development (AMED, JP20gm5010001), Osaka Kidney Bank (OKF19-0010), Shiseido Co., Ltd and KAGAMI Inc.
Competing Interests: A part of this study was funded by Shiseido Co., Ltd and KAGAMI Inc. TK has an equity in KAGAMI Inc. TK is an inventor on issued and applied patents (WO2020080484A1, PCT/JP2020/048977), which are related with this work. All other authors declare no competing interests.
(© 2021 The Authors.)
Databáze: MEDLINE