Assessing the longitudinal effects of high phosphate diet on cardiac & renal physiological measurements

Adaysha C. Williams, Lauren E. Yunker, and Alison J. Kriegel

The development of cardiovascular dysfunction secondary to renal disease is called Cardiorenal Syndrome Type 4. In advanced stages of chronic kidney disease, uremic toxins accumulate and are known to be associated with cardiac hypertrophy that precedes cardiac dysfunction. In previous studies performed by our lab, following 5/6 nephrectomy—a surgical excision rat model of human CRS4—uremic toxin, phosphate, is elevated in comparison to sham counterparts. Other evidence suggesting a role of phosphate in cardiac pathology includes a reduction in cell proliferation in rat embryonic cardiomyoblasts following 24-hours of incubation with inorganic phosphates, indicative of cellular pathology and while mimicking hyperphosphatemia of chronic kidney disease. With pathology seen in our renal-dependent in-vivo model and renal-independent in-vitro model, we hypothesize that a high phosphate diet leads to alterations in cardiac function independent of renal dysfunction. To investigate the impact of high circulating inorganic phosphate, we placed female SD rats on high phosphate diet (2% HiPi) for 7 weeks and performed echocardiography and renal ultrasound to assess physiological changes in the heart and kidney. Following 8 weeks of 2% HiPi diet, female rats had reduced body weight, heart weight, and heart to body weight ratio, as well as smaller left ventricular weight at endpoint compared to control rats (N=4-6; One-way ANOVA, p<0.05). The 2% HiPi female rats also had a drastic increase in left kidney weight and left kidney to body weight ratio (p<0.05). Despite differences in organ weight, weekly left ventricle echocardiography did not detect any significant changes in ejection fraction over the 7-week study. This study begins the groundwork for understanding the impact of high phosphate, independent of other uremic toxins, in cardiac function. Future studies plan to assess serum and urine levels pertinent to phosphate metabolism to changes in organ weights in the context of other functional parameters.