Shaking it off: loss of NHE3-mediated calcium reabsorption is compensated by the distal nephron

Abstract

Sodium reabsorption is tightly coupled to calcium reabsorption in the proximal tubule via the action of the Na⁺/H⁺ exchanger isoform 3 (NHE3). Poulsen et al. provide evidence of reduced proximal calcium reabsorption in kidney tubule–specific NHE3-deficient mice that is compensated distally, unaltered phosphate homeostasis, and NHE3 involvement in the hypocalciuric effect of thiazides. These results provide support that gastrointestinal NHE3 inhibitors, used for hyperphosphatemia treatment, are unlikely to cause long-term impact on bone mineralization.