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Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients

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Abstract

Background

Recently, we demonstrated that urinary angiotensinogen (AGT) levels are increased and reflect intrarenal renin–angiotensin system (RAS) status in pediatric patients with chronic glomerulonephritis. Therefore, this study was performed to test the hypothesis that urinary AGT (UAGT) levels provide a specific index of intrarenal RAS status associated with RAS blockade treatment in pediatric IgA nephropathy (IgAN) patients.

Methods

We measured plasma and UAGT levels and urinary transforming growth factor beta (TGF-β) levels, after which we performed immunohistochemical analysis of AGT, angiotensin II (Ang II), and TGF-β in 24 pediatric IgAN patients treated with RAS blockades for 2 years. Paired tests were used to analyze the changes from baseline to study end.

Results

Although there was no change in plasma AGT levels, UAGT and TGF-β levels were significantly decreased after RAS blockade, which was accompanied by the expression levels of AGT, Ang II, and TGF-β, as well as the magnitude of glomerular injury. Baseline UAGT levels positively correlated with diastolic blood pressure, urinary protein levels, scores for mesangial hypercellularity, and the expression levels of AGT, Ang II, and TGF-β in renal tissues.

Conclusions

These data indicate that UAGT is a useful biomarker of intrarenal RAS activation, which is associated with glomerular injury during RAS blockade in pediatric IgAN patients.

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Acknowledgments

The authors acknowledge technical assistance from Ms. Naomi Okamoto and Ms. Chizuko Yamamoto. This study was supported by JSPS KAKENHI Grant Numbers 23591569 and 26461612.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Pediatrics, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan

    Maki Urushihara, Takashi Nagai, Yukiko Kinoshita, Sato Nishiyama, Kenichi Suga, Natsuko Ozaki, Ariunbold Jamba, Shuji Kondo & Shoji Kagami

  2. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Hiroyuki Kobori

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  1. Maki Urushihara
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  2. Takashi Nagai
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  3. Yukiko Kinoshita
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  9. Hiroyuki Kobori
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Correspondence to Maki Urushihara.

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Urushihara, M., Nagai, T., Kinoshita, Y. et al. Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients. Pediatr Nephrol 30, 975–982 (2015). https://doi.org/10.1007/s00467-014-3028-8

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  • DOI: https://doi.org/10.1007/s00467-014-3028-8

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