Dietary sodium induces a redistribution of the tubular metabolic workload

Na+ excretion by the kidney varies according to dietary Na+ intake. We undertook a systematic study of the effects of dietary salt intake on glomerular filtration rate (GFR) and tubular Na+ reabsorption. We examined the renal adaptive response in mice subjected to 7 days of a low sodium diet (LSD) containing 0.01% Na+, a normal sodium diet (NSD) containing 0.18% Na+ and a moderately high sodium diet (HSD) containing 1.25% Na+. As expected, LSD did not alter measured GFR and increased the abundance of total and cell‐surface NHE3, NKCC2, NCC, α‐ENaC and cleaved γ‐ENaC compared to NSD. Mathematical modelling predicted that tubular Na+ reabsorption increased in the proximal tubule but decreased in the distal nephron because of diminished Na+ delivery. This prediction was confirmed by the natriuretic response to diuretics targeting the thick ascending limb, the distal convoluted tubule or the collecting system. On the other hand, HSD did not alter measured GFR but decreased the abundance of the aforementioned transporters compared to NSD. Mathematical modelling predicted that tubular Na+ reabsorption decreased in the proximal tubule but increased in distal segments with lower transport efficiency with respect to O2 consumption. This prediction was confirmed by the natriuretic response to diuretics. The activity of the metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK) was related to the changes in tubular Na+ reabsorption. Our data show that fractional Na+ reabsorption is distributed differently according to dietary Na+ intake and induces changes in tubular O2 consumption and sodium transport efficiency.This work was supported by the National Centre of Competence in Research Kidney control of homeostasis and a Swiss National Science Foundation grant 31003A 156736/1 to EF, 310030 143929/1 to JL and 31003A 155959 to CAW. KU received funding within the framework of IKPP2 from the EuropeanUnion's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 608847. (National Centre of Competence in Research Kidney control of homeostasis; 31003A 156736/1 - Swiss National Science Foundation; 310030 143929/1 - Swiss National Science Foundation; 31003A 155959 - Swiss National Science Foundation; 608847 - EuropeanUnion's Seventh Framework Programme for research, technological development and demonstration)Published versio