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 of the main ion transport systems involved in regulated Na⁺ renal reabsorption: the collecting duct Na-epithelial channel (ENaC) and the thick ascending loop of henle Na-K-2Cl cotransporter (NKCC2). Furthemore AMPK activity in the kidney is increased in rats under salt loading. We are trying to define the role of AMPK in salt renal handling by studying the renal phenotype in mice with genetic deletion of the AMPK catalytic subunit, isoform 2 (alpha-2 KO). Metabolic studies show these mice exhibit a tendency to a higher food and drink consumption and diuresis. Apart from these non significant observations, the renal function parameters studied were not different in the alpha-2 KO mouse. Then, we exposed mice to diets containing different Na⁺ contents, to evaluate renal sodium handling in the alpha-2 KO mouse. When exposed to a high salt diet (4% NaCl), alpha-2 KO mouse renal function parameters were indistinguishable from those in wild-type mice. We observed some differences in alpha-2 KO mouse response to Na⁺ deprivation, though none of these differences are significant yet (n=6): alpha-KO mice maintained an elevated glomerular filtration rate, and excrete a larger volume of more diluted urine. We have not found any difference regarding NKCC2 expression or activity in alpha-KO mice under none of the three sodium loads. In summary, alpha-2 KO mice do not exhibit a marked renal phenotype.