Uremic cardiomyopathy and muscle atrophy are associated with insulin resistance and contribute to chronic kidney disease (CKD)-induced morbidity and mortality. We hypothesized that restoration of levels would enhance exosome-mediated microRNA transfer to improve muscle wasting and cardiomyopathy that occur in CKD. Using next generation sequencing and qPCR, we found that CKD mice had a decreased level of in heart and skeletal muscle. We engineered an exosome vector that contained an exosomal membrane protein gene fused with a muscle-specific surface peptide that targets muscle delivery. We transfected this vector into muscle satellite cells and then transduced these cells with adenovirus that expresses to produce exosomes encapsulated (Exo/ ). Exo/ was injected once per week for 8 weeks into the tibialis anterior (TA) muscle of 5/6 nephrectomized CKD mice. Treatment with Exo/ resulted in increased expression of in skeletal muscle and heart. Overexpression of increased the skeletal muscle cross-sectional area, decreased the upregulation of FBXO32/atrogin-1 and TRIM63/MuRF1 and depressed cardiac fibrosis lesions. In the hearts of CKD mice, FoxO1 was activated, and connective tissue growth factor, fibronectin and collagen type I alpha 1 were increased. These responses were blunted by injection of Exo/ . Echocardiograms showed that cardiac function was improved in CKD mice treated with Exo/ . Overexpression of in muscle prevented CKD-induced muscle wasting and attenuated cardiomyopathy via exosome-mediated transfer. These results suggest possible therapeutic strategies for using exosome delivery of to treat complications of CKD.