Heart remodelling in CKD: heart hypertrophy, capillary/myocyte mismatch, myocardial fibrosis

Chronic kidney disease (CKD) patients have a substantially increased risk for cardiovascular disease. Marked cardiac remodelling, including myocardial fibrosis, hypertrophy, and decreased vascularisation is frequently observed in uremic patients as well as in animal models of CKD. Left ventricular (LV) hypertrophy, a well-known feature of renal failure, and LV mass have been correlated with survival in renal patients. Thus, renal disease obviously does not only affects cardiac morphology; it leads to LV systolic and diastolic dysfunction, all of which could be related to the increased incidence of sudden death. In adition to heart hypertrophy, insufficient or impaired angiogenesis can also lead to profound ventricular remodelling, heart dysfunction, and subsequent failure.

The underlying, complex pathogenesis of heart remodelling in CKD involves diverse, often interactive factors, including hemodynamic/volume-related factors, but also cellular and molecular mechanisms. The implication of signaling pathways and growth factors, proteases, and structural proteins are increasingly well understood. In this regard, we aim to identify new mediators contributing to heart hypertrophy like calcineurin activation (EHJ 2011) and fibroblast growth factor 23 (JCI 2011); and to capillary deficit like the soluble VEGF receptor sFlt-1 (JASN 2009), hyperphosphatemia (KI 2013) and decreased number of stem/progenitor cells (EHJ 2011).

For this purpose, we have been using the experimental model of 5/6 nephrectomy (remnant kidney model), which represents one of the most used animal models of progressive renal failure/chronic kidney disease by reduced nephron number. Apart from renal injury, these rats are characterized by a significant heart remodelling as observed in patients with CKD. Our studies take advantage of the fact that this model enables to investigate the influence of pharmacological and other factors on functional and morphological renal and cardiac parameters.