Hyperosmolarity drives hypertension and CKD--water and salt revisited

Nat Rev Nephrol. 2014 Jul;10(7):415-20. doi: 10.1038/nrneph.2014.76. Epub 2014 May 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agricultural Workers' Diseases / etiology*
  • Central America
  • Dehydration / complications*
  • Fructokinases / blood
  • Humans
  • Hypertension / etiology*
  • Kidney Diseases / complications
  • Osmolar Concentration*
  • Plasma*
  • Renal Insufficiency, Chronic / etiology*


  • Fructokinases
  • fructokinase