Acute Renal Failure (ARF) is frequently encountered in hospitalized patients where it is associated with increased mortality and morbidity notably affecting muscle wasting. Increased protein degradation has been shown to be the main factor of renal failure induced muscle atrophy, but the proteolytic pathways involved are poorly known. The Ubiquitin Proteasome System (UPS) is almost systematically activated in various catabolic situations, and the E3 ligases MuRF1 and MAFbx are generally up regulated in atrophying muscles. We hypothesized that activation of the E3 ligases MuRF1 and MAFbx may be one of the main fate in catabolic skeletal muscles from ARF animals. We used gentamicin-induced acute tubular necrosis in rats fed a high protein diet to promote acidosis. We first addressed the impact of ARF in the development of mild catabolic conditions. Using RT-PCR and immunoblotting, we then investigated the expression of the main muscle specific E3 ligases. We found that both muscle atrophy and UPS activation were induced with the development of ARF. In addition, the phasic muscles were more sensitive to 7-days ARF (-11 to -17%, P < 0.05) than the antigravity soleus muscle (-11%, NS), indicating a differential impact of ARF in the musculature. We observed an increased expression of the muscle-specific E3 ligases MuRF1 and MAFbx in phasic muscles that was highly correlated to the residual renal function of animals (R2 = 0.60, P < 0.01 and R2 = 0.60, P < 0.01 respectively). Conversely, we observed no variation in the expression of three other E3 ligases (Nedd4, Trim32 and Fbxo30/MUSA1). Altogether, our data indicate that MuRF1 and MAFbx are sensitive markers and potential targets to prevent muscle atrophy during ARF caused by toxic acute tubular necrosis