#5799 COMPENSATORY HYPERTROPHY OF THE KIDNEY CONTRIBUTES TO LOSS OF KLOTHO KIDNEY THROUGH PAKT SIGNALING

Abstract Background and Aims Chronic kidney disease (CKD) represents a significant public health burden worldwide, mainly driven by the increase of incidence associated risk factors like diabetes. Decreased renal Klotho expression is an early feature CKD, driving on circulating FGF23 phosphate. These alterations in mineral metabolism have direct negative impact progression dysfunction can cause bone alterations, vascular calcification heart failure. In parallel, during stages kidneys activate molecular mechanisms hypertrophy attempt to counteract loss function. The PI3K/Akt/mTOR pathway, activated growing insulin-like factor-1 (IGF-1) participates compensatory growth. aim present study investigate possible role PI3K/Akt activation levels hypertrophy. Method We generated mice model (UNX mice) which klotho parameters were analyzed. Furthermore, some treated with inhibitors pathway. vitro, proximal tubular epithelial human cells (PTEC) stimulated IGF-1 order effects determined. Results UNX pathway kidney, correlates expression. Moreover, showed both, plasma phosphate FGF23, decrease fractional excretion (% FEPi). Renal function, estimated BUN levels, was unaltered. Pharmacological inhibition restored decreased normalizing blood levels. PTEC induced decline expression, PI3K/AKT inhibitors. Conclusion overactivation modulates has Our findings constitute important breakthrough research new therapeutic targets maintain it may be useful treatment patients.