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Hyperosmolarity drives hypertension and CKD—water and salt revisited

Nature Reviews Nephrology volume 10, pages 415–420 (2014)Cite this article

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Abstract

An epidemic of chronic kidney disease (CKD) in Mesoamerica is providing new insights into the mechanisms by which salt and water might drive hypertension and CKD. Increasingly, evidence suggests that recurrent dehydration and salt loss might be a mechanism that causes CKD, and experimental studies suggest a key role for increased plasma osmolarity in activating both intrarenal (polyol–fructokinase) and extrarenal (vasopressin) pathways that drive renal injury. Thus, we propose that water and salt might influence blood pressure and kidney disease through the timing and combination of their intake, which affect plasma osmolarity as well as intrarenal and extrarenal mechanisms of renal injury. The type of fluid intake might also be important, as fluids containing fructose can trigger activation of these pathways. Future studies should investigate the effects of salt, sugar and fluid intake on plasma osmolarity as a potential pathogenetic mechanism in renal injury and high blood pressure.

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Figure 1: Chronic tubulointerstitial fibrosis in Mesoamerican nephropathy.
Figure 2: Physiological and pathophysiological effects of water depletion on the kidney.

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Acknowledgements

R.J.J.'s research work is funded by the University of Colorado, Denver, CO, USA, and NIH grant funding. L.G.S.-L.'s work is funded by CONACyT Mexico (No. 133232).

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Authors and Affiliations

  1. Division of Nephrology, Department of Veteran Affairs, Eastern Colorado Health Care System, 12700 East 19th Avenue, Room 7015, Aurora, 80045, CO, USA

    Richard J. Johnson

  2. Universidad del Zulia, Instituto Venezolano de Investigaciones Científicas (IVIC)-Zulia, Maracaibo, Venezuela

    Bernardo Rodriguez-Iturbe

  3. Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO, USA

    Carlos Roncal-Jimenez, Miguel A. Lanaspa & Takuji Ishimoto

  4. Mitsubishi Tanabe-Kyoto (TMK) project, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Takahiko Nakagawa

  5. Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Ricardo Correa-Rotter

  6. Program on Work, Environment and Health in Central America (SALTRA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica

    Catharina Wesseling

  7. INSERM Unité Mixte de Recherche, (UMR)-S 1138/Equipe 2, Centre de Recherche des Cordeliers, Paris, France

    Lise Bankir

  8. Laboratory of Renal Physiopathology, Intituto Nacional de Cardiología Ignacio Chavez, Mexico City, Mexico

    Laura G. Sanchez-Lozada

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Contributions

R.J.J., L.B. and L.G.S.-L. researched the data for the article. All authors contributed to the discussion of the article's content, after which R.J.J., B.R.-I., L.B. and L.G.S.-L. wrote the manuscript. R.J.J., B.R.-I., T.I., T.N., R.C.-R., C.W., L.B. and L.G.S.-L. edited the manuscript before submission.

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Correspondence to Richard J. Johnson.

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Competing interests

R.J.J. and M.A.L. are inventors on patent applications related to blocking fructokinase in the treatment of kidney disease and metabolic syndrome from the University of Colorado (US2013/0195886 and US2013/0224218). R.J.J. is on the Scientific Advisory Board of Amway, the Scientific Board of XORT Therapeutics and of Rivermend Health. R.J.J. has also received research funding from Danone Research and Amway. R.J.J., C.R. J., M.A.L. and L.G.S. L. are members of Colorado Research Partners. The other authors declare no competing interests.

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Johnson, R., Rodriguez-Iturbe, B., Roncal-Jimenez, C. et al. Hyperosmolarity drives hypertension and CKD—water and salt revisited. Nat Rev Nephrol 10, 415–420 (2014). https://doi.org/10.1038/nrneph.2014.76

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