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Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin

  • Integrative physiology
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Abstract

The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS−/−) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS−/− and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS−/− mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.

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Acknowledgements

The present study was supported by grants from The Danish Strategic Research Council, The Novo Nordisk Foundation and the Danish Research Council for Health and Disease, by the Region of Southern Denmark. The authors thank Lis Teusch and Lene Andersen for the skillful technical assistance.

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Authors and Affiliations

  1. Research Unit for Cardiovascular and Metabolic Prevention, Department of Endocrinology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense C, Denmark

    Christina Oxlund & Ib A. Jacobsen

  2. Institute of Physiology, University of Regensburg, Regensburg, Germany

    Birgül Kurt & Ilona Schwarzensteiner

  3. Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Mie R. Hansen, Mette Stæhr, Per Svenningsen, Pernille B. Hansen, Anne D. Thuesen, Gitte R. Hinrichs & Boye L. Jensen

  4. Department of Urology, Odense University Hospital, Odense, Denmark

    Anja Toft

  5. Department of Nephrology, Odense University Hospital, Odense, Denmark

    Claus Bistrup

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  1. Christina Oxlund
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Correspondence to Christina Oxlund.

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Oxlund, C., Kurt, B., Schwarzensteiner, I. et al. Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin. Pflugers Arch - Eur J Physiol 469, 655–667 (2017). https://doi.org/10.1007/s00424-017-1938-6

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  • DOI: https://doi.org/10.1007/s00424-017-1938-6

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