Renal sodium reabsorption is a high energy-consuming process. AMP-activated kinase (AMPK), a key regulator of cell metabolic status has been recently linked to the regulation of two ion transport systems involved in Na⁺ renal reabsorption: the collecting duct Na-epithelial channel (ENaC) and the Na-K-2Cl cotransporter (NKCC2) in the loop of Henle (TAHL). Furthermore, AMPK activity in the kidney is increased in rats under salt loading. We are trying to define the role of AMPK in kidney function by studying mice with genetic deletion of the AMPK catalytic subunit, isoform 1 (alpha-1 KO). Metabolic studies showed these mice exhibit a tendency to excrete less urine, which is twice more concentrated than in wild-type mice (non-significant, n=8), despite there is no change in glomerular filtration rate or Na⁺ and K⁺ renal handling. Then, we evaluated renal sodium handling in the alpha-1 KO mouse. When exposed to a high salt (4% NaCl) or sodium-deficient (0.02%) diets, alpha-1 KO mouse renal function parameters were indistinguishable from those observed in wild-type mice. We found a marked increased in NKCC2 total expression in alpha-1 KO mice. On the other hand, NKCC2 phosphorylation was reduced. At this point we cannot discriminate the primary change. While AMPK alpha-1 KO mice do not show a marked renal phenotype, which may be partially explained by a significant upregulation of alpha-2 AMPK, our finding that alpha-1 AMPK might be involved in regulating NKCC2 expression/activity levels reinforces our previous hypothesis for a role of this kinase in the TAHL.