A chronic canine model of heart failure and renal insufficiency (cardiorenal syndrome)

Abstract

IntroductionThe co‐existence of renal insufficiency (RI) in patients with heart failure (HF) often referred to as “cardiorenal syndrome” (CRS), carries an extremely poor prognosis. Understanding the pathophysiology of CRS and development of new therapeutics that address this complex syndrome are hindered by lack of appropriate animal models.ObjectiveWe tested the hypothesis that a unilateral nephrectomy with sustained increase in contralateral renal vein pressure in dogs with established HF would lead to RI with a rise in serum creatinine (sCr) and blood urea nitrogen (BUN) and can serve as a model of CRS.MethodsSix dogs with coronary microembolization‐induced heart failure (LV ejection fraction, EF <30%) were studied. A right nephrectomy was performed in all dogs and the distal left renal vein was banded to increase proximal renal vein pressure from ~10 to ~35 mmHg. sCr and BUN were measured preoperatively, and at 1, 2, 3, 4, 7, and 8 weeks thereafter. A diuretic challenge (DC) was administered (furosemide 80 mg IV) to all dogs 3–4 weeks after surgery. sCr and BUN were measured before and 5 hours after DC.ResultsAll dogs developed RI as evidenced by a significant rise in sCr and BUN that persisted for 8 weeks (Table). DC increased sCr from 1.3±0.1 to 1.6±0.1 mg/dL (p<0.003) and BUN from 24±1.8 to 33±1.8 mg/dL (p<0.001).ConclusionsThe results describe a reproducible canine model of chronic HF and RI (model of CRS) that responds to DC in a manner consistent with the response of CRS patients to IV diuretics.