Characterization of Kidney Function in a Canine Model of Cardiorenal Syndrome
Hani Sabbah HN, Gupta RC, and Lanfear D. Characterization of Kidney Function in a Canine Model of Cardiorenal Syndrome. Eur J Heart Fail 2019; 21:577.
Eur J Heart Fail
Background: The co-existence of renal insuffciency in patients with heart failure (HF) often referred to as "cardiorenal syndrome" (CRS), carries a poor prognosis. Understanding the pathophysiology of CRS and the need to develop new therapeutics that address this complex syndrome are often hindered by lack of appropriate animal models. In the present study, we provide further characterization of kidney function in a chronic canine model of CRS developed in our laboratories to help defne the differences in this model when compared to a canine model of HF with preserved renal function. [Table Presented] Methods: Studies were performed in 15 dogs with coronary microembolization-induced HF. In 8 of the 15 dogs, CRS was produced by performing a unilateral nephrectomy and by applying a stenosis to the contralateral renal vein to simulate elevated venous pressures. LV ejection fraction (LVEF), urinary protein, urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase associated lipocalin (NGAL) and plasma cystatin-C were measured in all 15 dogs and in 6 normal dogs. Each dog was also given a diuretic challenge (DC) consisting of an intravenous injection of 80 mg of furosemide and pCr was measured before and one hour after the injection. Results: LVEF was similar in HF dogs and CRS dogs (34±1 vs. 33±2 %). Urinary protein, pCr, NGAL, KIM-1 and cystatin-C were similar in NL and HF dogs but increased significantly in CRS dogs (Table). DC had no effect on pCr in HF (0.84±0.06 vs. 0.90±0.07 mg/dL) but increased significantly in CRS dogs (1.21±0.04 vs. 1.41±0.04 mg/dL, p<0.05). Conclusions: Results of the study indicate that the canine model of CRS manifest similar abnormalities seen in patients with HF and compromised renal function. The CRS model may be useful for exploring pathophysiological aspects of CRS and can serve a tool for assessing the effects of therapeutic/pharmacologic interventions targeting patients with HF and compromised renal function.