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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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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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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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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DOI: https://doi.org/10.1038/nrneph.2014.76
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