Four weeks of dietary potassium restriction causes distal convoluted tubule remodeling

Previous studies have described a ‘renal potassium switch’ within the distal nephron that turns on the thiazide‐sensitive Na‐Cl cotransporter (NCC) in the distal convoluted tubule (DCT) in response to low potassium intake and off in response to high potassium intake. Studies using genetically modified mice indicate that decreased NCC activity is associated with decreased DCT length and mass; increased NCC activity is associated with increased, DCT length and mass. The aim of our study was to test whether dietary potassium intake causes the DCT remodeling physiologically. Male C57Bl/6 mice were provided either control potassium diet or low potassium diet for four weeks and blood and kidneys were harvested. To determine the length of the DCT in three dimensions, we used Ethyl‐cinnamate‐based optical clearing, combined with whole‐mount immunolabeling, confocal microscopy and three‐dimensional morphometric analysis. Mice on low potassium diet for four weeks were severely hypokalemic (plasma potassium <2 mM) compared with mice on control diet (4.1 mM). Western‐blot analysis of the whole kidney confirmed that total and phosphorylated NCC were higher in mice on low potassium diet, compared to mice on control diet. By immunolabeling with pThr53‐NCC antibody, we visualized the DCTs in optically cleared kidney slices. Three‐dimensional morphometric analysis suggested that four‐weeks of low potassium diet (487±16 μm, n=5) increased DCT length by 13% compared to NK diet (431±3 μm, n=3). Our results indicate that the DCT remodels physiologically to maintain potassium homeostasis. Additional animals are currently being studied. Support or Funding Information LeDucq Fondation, KidneyCure