Single genetic trigger model of CKD-associated cardiac remodeling in podocyte-specific MafB knockout mice

Chronic kidney disease (CKD) causes systemic complications that contribute to renal-cardiac disease (RCD), but experimental models that reproducibly link defined renal injury to cardiac remodeling and CKD-associated complications remain limited. Here, we examined whether podocyte-specific MafB knockout mice, in which glomerular injury is genetically induced, can serve as a single-gene-driven model for studying renal-cardiac interactions. Mice ( Mus musculus ) with a C57BL/6 background were used in this study. MafB -deficient mice developed progressive glomerulosclerosis and tubulointerstitial injury, followed by cardiac hypertrophy and fibrosis. These cardiac changes were accompanied by CKD-associated systemic abnormalities, including hypertension, renal anemia, and elevated serum fibroblast growth factor 23 levels. Echocardiographic and hemodynamic analyses supported the development of cardiac remodeling during CKD progression. Pharmacological intervention with angiotensin receptor–neprilysin inhibition partially improved disease-related parameters, including blood pressure, cardiac hypertrophy, renal function, and the urinary albumin levels. These findings suggest that podocyte-specific MafB knockout mice provide a genetically defined experimental setting in which CKD, cardiac remodeling, hypertension, renal anemia, and mineral metabolism abnormalities develop in sequence. This model may complement conventional multi-hit RCD models and may be useful for investigating kidney–heart interactions and evaluating therapeutic strategies for cardiovascular complications secondary to renal injury.