*3.2. Chemically Induced Models*

Surgical methods to induce CKD associated with cardiovascular changes are often accompanied by a high mortality and require well-trained surgeons. Thus, e fforts have been made to establish non-surgical techniques for CKD induction. One option is to apply orally administered adenine, which is metabolized to 2,8-dihydroxyadenine, and which in turn precipitates as crystals in the renal proximal tubular epithelium causing inflammation and fibrosis, ultimately leading to CKD. Indeed, mice treated with adenine developed symptoms of the cardiorenal syndrome, in particular cardiac hypertrophy, impaired cardiac function, as well as increased fibrosis [97].

An additional chemically induced model for murine CKD-CVD was achieved in mice via a single injection of cisplatin and subsequent feeding of a high-phosphate diet. CKD was confirmed by decreased creatinine clearance, development of interstitial kidney fibrosis, hyperphosphatemia, high plasma levels of PTH and FGF23 and low levels of plasma calcitriol and αKlotho. The mice developed LVH and cardiac fibrosis. This model resembles the transition from acute kidney injury to chronic renal failure and thus displays a promising approach to study underlying mechanisms in humans [93].
