Catching chronic kidney disease (CKD) early is critical – patients have a heightened risk of life-threatening cardiovascular diseases and increasingly progress to end-stage kidney disease. But despite an estimated 850 million cases throughout the world (1), the early referral of patients with CKD remains a challenge due to inadequate tests.
In 2016, we reported on a breakthrough in the quest to identify an effective biomarker for early CKD diagnosis: a team from Osaka University found that levels of D-amino acids could predict progression to end-stage kidney disease (2). However, at the time, first author Tomonori Kimura told us “the D-amino acid world is a mystery,” clouding the potential clinical applications of their discovery. Three years on from their initial research, how close have the researchers come to solving that mystery?
D-amino acids are the enantiomers of L-amino acids and – although only trace amounts are present in humans – they are gaining attention as potential biomarkers for a number of diseases. “In our previous study, we saw that the level of D-serine in the blood was well correlated with the estimated glomerular filtration ratio (GFR), which is a key marker of kidney function,” says Kimura. In a new study, the team delved deeper into the diagnostic value of D-serine and applied micro-two-dimensional high-performance liquid chromatography (2D-HPLC) to assess its efficacy as an early indicator of CKD.
Their discovery? That D-serine levels in the blood of CKD patients correlated with GFR at a rate equal to or better than existing markers of kidney disease. In addition, the level of D-serine in the urine provided important information on kidney function other than GFR. “To screen for CKD, it is best to monitor D-serine in both the blood and the urine; it can serve as a dual biomarker for both the prediction of kidney function and the detection of CKD,” Kimura explains.
Current markers for the estimation of GFR include serum creatinine and serum cystatin C – but both are affected by other factors, such as muscular mass. “One of the main advantages of using 2D-HPLC to measure D-serine is its sensitivity and precision – the ability to potentiate absolute quantification removes any small variations in measurements.”
The new research found that the kidney’s balance between excretion and reabsorption of amino acids is controlled by chiral selectivity. This makes the reabsorption of D-serine sensitive to the presence of CKD, allowing testing to distinguish patients with the disease from those without. As we take one step closer to unravelling the mystery of D-amino acids, Kimura believes that there is plenty of potential to fulfill: “Because CKD is prevalent in patients with lifestyle-related diseases, such as diabetes, hypertension, and cardiovascular disease, understanding D-serine is likely to improve prognosis and therapy discovery in these, too.”
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References
- A Hesaka et al., “D-Serine reflects kidney function and diseases”, Sci Reports, 9, 5104 (2019). PMID: 30911057. M Schubert, “A New Angle on CKD”, The Pathologist, 22, 9 (2016). Available at: https://bit.ly/2FTmn6s.
