The incidence of chronic kidney disease (CKD) complicated with cardiovascular disease (CVD) is increasing day by day. CVD complication is a significant risk factor for the progression and poor prognosis of CKD. However, in terms of clinical diagnosis, treatment, and pathophysiological mechanism, there are still many things that are not clear about CKD combined with CVD. In this article, we observed the abnormal expression of long non-coding RNA ZFAS1 (lncRNA ZFAS1) in the heart and renal tissues of CKD mice, which may a target for nephropathy with CVD. We observed that exosomes containing lncRNA ZFAS1 induced fibrosis in the heart via the wnt4/β-catenin signal pathway. Luciferase assay reported that lncRNA ZFAS1 could bind with microRNA-4711-5p (miR-4711-5p), and wnt4 was a target of miR-4711-5p. In conclusion, lncRNA ZFAS1 from HCM could promote cardiac fibrosis through WNT/β-catenin signal via exosome pathways, which provided an underlying mechanism in the cardiac fibrosis from CKD.