Abstract 084: Growth Stress And Cardiorenal Syndrome: Effect Of Renal Insufficiency On Blood Pressure And Cardiac Remodeling In Juvenile Rats

Abstract

Pediatric patients living with chronic kidney disease (CKD) can experience many of the comorbidities associated with CKD in adults including hypertension and cardiovascular (CV) pathology, as well as impaired somatic growth. The goal of this study was to understand how CKD impacts blood pressure and cardiac remodeling during a period of rapid somatic growth. We hypothesized that renal insufficiency in juvenile rats would lead to both impaired growth and cardiac hypertrophy, demonstrating that it is an appropriate model for studying mechanisms of cardiorenal syndrome (CRS) in pediatric patients. Young male Sprague Dawley rats (4-5 weeks of age) were weighed and underwent nuclear magnetic resonance imaging to assess body mass and composition and were then randomized to naïve (n=6), Sham (n=9) or 5/6 nephrectomy (5/6Nx; n=11) groups. Rats underwent echocardiography before surgery and at the end of the 4 week study. Anesthetized blood pressure was measured via the carotid artery. Tissues were collected weighed and stored for histological and molecular analysis. Results presented as mean±SEM, one-way ANOVA and p<0.05. There were no differences in body weights or composition between groups at the start of the study. No differences were measured between naïve and sham groups throughout the study. The 5/6Nx rats experienced less somatic growth than sham rats. Final body weight was lower in 5/6Nx rats than sham rats (229.2±4.0 vs. 229.6±17g). Similarly, tibialis length (TL) was smaller in 5/6Nx rats than sham rats (35.97±0.64 vs. 38.32±0.22 mm). The 5/6Nx group experienced a large increase in SBP when compared to sham animals (195.2±6.54 vs. 123.8±4.53 mmHg). Heart weight was higher in 5/6Nx vs. sham rats, despite the smaller body size. This difference was even more apparent when heart weight was normalized to TL (5/6Nx, 0.34± 0.10 vs. sham, 0.27±0.01 g/cm). These studies indicate that 5/6Nx surgery in juvenile SD rats can recapitulate characteristics of pediatric CRS and CKD-related growth impairment. Adult male 5/6Nx SD rats in our prior studies developed cardiac hypertrophy in the absence of hypertension. These results suggest that the added stress of growth during renal insufficiency can drive both hypertension and cardiac hypertrophy in juvenile rats.