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Background: The effects of sodium (Na+) intakes on renal handling of potassium (K+) are insufficiently studied., Methods: We assessed the effect of Na+ on renal K+ handling in 16 healthy males assigned to three 7-day periods on low salt diet [LSD, 3 g sodium chloride (NaCl)/day], normal salt diet (NSD, 6 g NaCl/day) and high salt diet (HSD, 15 g NaCl/day), with constant K+ intake. Contributions of distal NaCl co-transporter and epithelial Na+ channel in the collecting system on K+ and Na+ handling were assessed at steady state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively., Results: Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 mL/min under LSD to 187.00 ± 49.10 under HSD (P = 0.005). The 24-h K+ excretion remained stable on all Na+ intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD; and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h) and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all three diets., Conclusions: Neither spontaneous nor diuretic-induced K+ excretion was influenced by Na+ intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal Na+ handling was dependent on dietary Na+ intake., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Key Points: Body Na + content is tightly controlled by regulated urinary Na + excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na + intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na + intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na + transporters all along the kidney tubule. Low dietary Na + intake increased Na + reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments. High dietary Na + intake decreased Na + reabsorption in the proximal tubule and increased it in distal segments with lower energetic efficiency. The abundance of apical transporters and Na + delivery are the main determinants of Na + reabsorption along the kidney tubule. Tubular O 2 consumption and the efficiency of sodium reabsorption are dependent on sodium diet., Abstract: 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 O 2 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 O 2 consumption and sodium transport efficiency., (© 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)