Effects of a high-sodium/low-potassium diet on renal calcium, magnesium, and phosphate handling

The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na⁺ reabsorption via the Na⁺-Cl^- cotransporter (NCC). A diet containing high salt (NaCl) and low K⁺ activates NCC, thereby causing Na⁺ retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca²⁺) and magnesium (Mg²⁺) levels, we hypothesized that dietary Na⁺ and K⁺ intake affects Ca²⁺ and Mg²⁺ transport in the DCT. Therefore, the present study aimed to investigate the effect of a high-Na⁺/low-K⁺ diet on renal Ca²⁺ and Mg²⁺ handling. Mice were divided in four groups and fed a normal-Na⁺/normal-K⁺, normal-Na⁺/low-K⁺, high-Na⁺/normal-K⁺, or high-Na⁺/low-K⁺ diet for 4 days. Serum and urine were collected for electrolyte and hormone analysis. Gene and protein expression of electrolyte transporters were assessed in kidney and intestine by qPCR and immunoblotting. Whereas Mg²⁺ homeostasis was not affected, the mice had elevated urinary Ca²⁺ and phosphate (P_i) excretion upon high Na⁺ intake, as well as significantly lower serum Ca²⁺ levels in the high-Na⁺/low-K⁺ group. Alterations in the gene and protein expression of players involved in Ca²⁺ and P_i transport indicate that reabsorption in the proximal tubular and TAL is affected, while inducing a compensatory response in the DCT. These effects may contribute to the negative health impact of a high-salt diet, including kidney stone formation, chronic kidney disease, and loss of bone mineral density.