{"p"=>{"__content__"=>"The sodium-hydrogen exchanger isoform 3 (NHE3) is a critical mediator of proximal tubule and thick ascending limb Na reabsorption and H/NH secretion, yet the physiological implications of its upregulation during low K intake remain poorly understood. We hypothesized that renal NHE3 is important for the acid-base response during K depletion. To test this, we utilized kidney-specific NHE3 knockout (NHE3) mice. Following 10 days of a K-deficient diet (< 30 ppm), NHE3 mice exhibited exacerbated hypokalemia compared to control mice, despite near complete elimination of urinary K excretion and comparable levels of ROMK and BKα protein abundance in both genotypes. Control and NHE3 mice developed hypernatremia secondary to a urinary concentrating defect; however, this was associated with a ~ 2-fold greater fluid intake in NHE3 mice. These effects occurred without changes in glomerular filtration rate. Both genotypes developed metabolic acidosis, which was significantly more severe in NHE3 mice. This exacerbated acidosis correlated with a ~ 60% lower mRNA expression of glutamine synthetase and a lower urinary NH/creatinine ratio. Furthermore, early histopathological signs of hypokalemic nephropathy were observed exclusively in some of the NHE3 mice. Our findings demonstrate that renal NHE3 attenuates the severity of hypokalemia and metabolic acidosis during K restriction, possibly via NH formation/transport, which might accelerate the development of hypokalemic nephropathy.", "sup"=>[{"__content__"=>"+"}, {"__content__"=>"+"}, {"__content__"=>"+"}, {"__content__"=>"+"}, {"__content__"=>"+"}, {"__content__"=>"KS−KO"}, {"__content__"=>"+"}, {"__content__"=>"KS−KO"}, {"__content__"=>"+"}, {"__content__"=>"KS−KO"}, {"__content__"=>"KS−KO"}, {"__content__"=>"KS−KO"}, {"__content__"=>"+"}, {"__content__"=>"KS−KO"}, {"__content__"=>"+"}, {"__content__"=>"+"}], "sub"=>[{"__content__"=>"4"}, {"__content__"=>"4"}, {"__content__"=>"4"}]}}