Abstract 1484: New Insights into the Kidney-Heart Connection: Mild Renal Insufficiency Induces Cardiac Fibrosis and Diastolic Dysfunction Followed by Late Systolic Impairment
Background: Reduced renal function (FX) increases CV morbidity and mortality by unclear mechanisms. We previously reported that mild reductions in renal FX produced by unilateral nephrectomy (NX) increase myocardial collagen content and induce alterations in LV gene profiles in the absence of hypertension (HTN) or volume overload (VO) Here we hypothesize that such alterations progress and result in diastolic and systolic impairment.
Methods: Cardiorenal FX and structure were assessed in Wistar rats, sham (S) at 4 weeks (wk; n=10) and at 16 wk (n=10) and also at 4 wk (n=9) and 16 wk (n=9) after NX. At 4wk GFR, Na and water excretion, plasma BNP, plasma renin activity (PRA), and aldosterone (Aldo) were assessed. By echo, LV mass, EF, circumferential systolic strain (Cs), early (Csr-E) and late (Csr-A) diastolic strain rates and ratio were assessed by echo speckle tracking. Cardiac fibrosis by picrosirius red staining was also determined.
Results: At 4wk glomerular hypertrophy was observed in NX (p<0.001) and GFR tended to decrease compared to S. Na and water excretions were not different between groups with no activation of PRA, Aldo or BNP. Blood pressure (BP), EF, LV mass, Cs did not differ between the groups. However, Csr-E and Csr-E/A ratio were significantly lower in NX group (S:6.4±0.5, NX:5.2±0.8 and S:1.8±0.5, NX:1.2±0.4;p<0.05 for both) consistent with diastolic dysfunction (DD). The LV of NX had greater fibrosis compared to S (p<0.001). At 16wk, LV mass was significantly higher in NX (S:1.0±0.1, NX:1.3±0.3 g,p<0.001), with a mild decrease in EF (S:79±4, NX:74±3,p<0.005), Cs (S:19.8±2.8, NX:16.2±1.8,p<0.005), and further decrease of Csr-E and Csr-E/A ratio (S:5.7±1.3, NX:4.5±0.6, and S:1.52±0.37, NX:0.98±0.4;p<0.05). In NX there was persistent LV fibrosis (p<0.001).
Conclusion: Even mild experimental renal insufficiency produced by NX results in early cardiac fibrosis and DD independent of neurohumoral activation, HTN, or VO. Furhtermore, at 16wk after NX there is progressive impairment of diastolic and systolic FX with LV hypertrophy. These studies support a kidney-heart connection in early renal dysfunction resulting in progressive ventricular dysfunction, remodeling and fibrosis.