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N-Acetyl-seryl-aspartyl-lysyl-proline is a potential biomarker of renal function in normoalbuminuric diabetic patients with eGFR ≥ 30 ml/min/1.73 m2

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Abstract

Background

A biomarker, by which we can predict alterations of renal function in normoalbuminuric diabetic patients, is not available. Here, we report that endogenous anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) represents a potential biomarker to predict alterations in eGFR in normoalbuminuric diabetic patients.

Methods

We analyzed 21 normoalbuminuric diabetic patients with eGFR ≥ 30 ml/min/1.73 m2 and measured AcSDKP levels in first morning void urine. We divided patients into two groups based on the median values: low or high urinary AcSDKP groups (uAcSDKP/Crlow or uAcSDKP/Crhigh). At baseline, no significant differences in sex, age, HbA1c, BMI, serum creatinine levels, etc., were observed between the two groups.

Results

During ~ 4 years, the alteration in eGFR [ΔeGFRop (ΔeGFR observational periods)] was significantly stable in uAcSDKP/Crhigh group compared with uAcSDKP/Crlow group over time (P = 0.003, χ2 = 8.58). We also evaluated urine kidney injury molecule-1 (uKim-1) levels and found that ΔeGFRop was also stable in low uKim-1 group compared with high uKim-1 group over time (P = 0.004, χ2 = 8.38). Patients who fulfilled the criteria for both uAcSDKP/Crhigh and uKim-1low exhibited stable ΔeGFRop (P < 0.001, χ2 = 30.4) when compared to the remaining patients. Plasma AcSDKP (P = 0.015, χ2 = 5.94) and urine β2-microglobulin (P = 0.038, χ2 = 4.31) also display weak but significant predictor of ΔeGFRop as well.

Conclusion

AcSDKP represents a potentially useful biomarker to predict alterations in the renal function of patients with diabetes presenting normoalbuminuria.

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Acknowledgments

Keizo Kanasaki and Daisuke Koya received lecture fees from Mitsubishi Tanabe Pharma. Mitsubishi Tanabe Pharma donated to Kanazawa Medical University but was not directly associated with this project. Boehringer Ingelheim, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical contributed to establishing the Division of Anticipatory Molecular Food Science and Technology. Keizo Kanasaki is currently engaged in a consultancy agreement contract with Boehringer Ingelheim. This work was partially supported by grants from the Japan Society for the Promotion of Science to Megumi Kanasaki (24790329), Munehiro Kitada (24591218), Takako Nagai (24659264), Keizo Kanasaki (23790381 and 26460403), and Daisuke Koya (25282028 and 25670414); research grants from the Japan Research Foundation for Clinical Pharmacology to Keizo Kanasaki (2011); and a Takeda visionary research grant to Keizo Kanasaki (2013). This work was partially supported by Grants for Collaborative Research awarded to Daisuke Koya (C2012-1 and C2014-4) and Grants for Promoted Research awarded to Keizo Kanasaki (S2013-13, S2014-4, and S2015-3) from Kanazawa Medical University. This work was also supported by Grants for Assist KAKEN to Kyoko Nitta (K2015-7, K2017-14, and K2018-15). Also this research is partially supported by the “Translational Research Network Program” from Japan Agency for Medical Research and Development, AMED for Keizo Kanasaki (#151m0103009j0004).

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Authors and Affiliations

  1. Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Kyoko Nitta, Takako Nagai, Yuiko Mizunuma, Munehiro Kitada, Atsushi Nakagawa, Keizo Kanasaki & Daisuke Koya

  2. Internal Medicine, Division of Nephrology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan

    Masao Toyoda

  3. Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Masaru Sakurai

  4. Nishiumeda Clinic for Asian Medical Collaboration near JR Osaka Station, Maruito Nishi Umeda Building 3F, 3-3-45, Umeda Kita-ku, Osaka, 530-0001, Japan

    Masakazu Haneda

  5. Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Munehiro Kitada, Keizo Kanasaki & Daisuke Koya

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  1. Kyoko Nitta
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  2. Takako Nagai
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  3. Yuiko Mizunuma
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  10. Daisuke Koya
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Correspondence to Keizo Kanasaki.

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Authors declare no conflict of interest in this study.

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Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.

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All procedures performed in studies involving human participants were in accordance with the Human Ethics Committee of Kanazawa Medical University at which the studies were conducted (IRB approval number R199) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Nitta, K., Nagai, T., Mizunuma, Y. et al. N-Acetyl-seryl-aspartyl-lysyl-proline is a potential biomarker of renal function in normoalbuminuric diabetic patients with eGFR ≥ 30 ml/min/1.73 m2. Clin Exp Nephrol 23, 1004–1012 (2019). https://doi.org/10.1007/s10157-019-01733-6

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