Chronic Nicotine Exposure Reduces Klotho Expression And Triggers Different Renal And Hemodynamic Responses In Klotho-Haploinsufficient Mice

The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium-phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal klotho expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (klotho+/+) mice, klotho-haploinsufficient (klotho+/−) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal klotho expression in klotho+/+ and klotho+/− mice, as well as with a reduction in the glomerular filtration rate in klotho+/+ mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced...