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Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy

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Abstract

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

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Acknowledgements

Funding was provided by Beijing Municipal Natural Science Foundation (Grant No. 7152127).

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Authors and Affiliations

  1. Graduate School of Peking Union Medical College, Beijing, China

    Zheng Zhang, Shi-min Jiang, Gu-ming Zou & Wen-ge Li

  2. Department of Nephrology, China-Japan Friendship Hospital, Yinghua East Street No. 2, Chaoyang District, Beijing, China

    Zheng Zhang, Shi-min Jiang, Ye-ping Ma, Pei-lin Dai, Yi-ning Wang, Gu-ming Zou, Hong-mei Gao, Yue Yang & Wen-ge Li

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  1. Zheng Zhang
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Correspondence to Yue Yang or Wen-ge Li.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Zhang, Z., Jiang, Sm., Ma, Yp. et al. Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy. Mol Cell Biochem 453, 103–110 (2019). https://doi.org/10.1007/s11010-018-3435-4

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  • DOI: https://doi.org/10.1007/s11010-018-3435-4

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