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Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease

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An Erratum to this article was published on 26 September 2013

Abstract

Background

Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD.

Methods

A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204).

Results

Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = −0.275) and Hb (P < 0.005, r = −0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = −0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = −0.148).

Conclusion

Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.

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Acknowledgments

This work was supported by the Japan Osteoporosis Foundation, Japanese Kidney Foundation, Kochi Organization for Medical Reformation and Renewal (to YT), and a grant from the Ministry of Education, Science, Culture and Sports of the Japan government (to YS, KI, KO, SF, and YT). We thank Ms. Reiko Matsumoto, Ms. Akiko Takano, and Ms. Sekie Saito for their technical assistance.

Conflict of interest

All the authors have declared no competing interest.

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nephrology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan

    Kazu Hamada, Yoshinori Taniguchi, Yoshiko Shimamura, Kosuke Inoue, Koji Ogata, Masayuki Ishihara, Taro Horino, Shimpei Fujimoto & Yoshio Terada

  2. Department of Internal Medicine, Kochi Red Cross Hospital, Kochi, Japan

    Takashi Ohguro & Yukio Yoshimoto

  3. Department of Urology and Internal Medicine, Kochi-Takasu Hospital, Kochi, Japan

    Mika Ikebe & Kenji Yuasa

  4. Clinical Trial Center, Kochi University School of Medicine, Kochi, Japan

    Eri Hoshino & Tatsuo Iiyama

  5. Department of Endocrinology and Hypertension, Tokyo Women’s Medical University, Tokyo, Japan

    Atsuhiro Ichihara

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  1. Kazu Hamada
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Correspondence to Yoshio Terada.

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Hamada, K., Taniguchi, Y., Shimamura, Y. et al. Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease. Clin Exp Nephrol 17, 848–856 (2013). https://doi.org/10.1007/s10157-013-0803-y

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  • DOI: https://doi.org/10.1007/s10157-013-0803-y

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