1. Intern Name: Phillip Witcher
Intern Major(s): Biochemistry
Mentor Name: Shoji Ichikawa, Ph.D.
Mentor Department: Medicine / Endocrinology
Poster Title: Investigating Phosphate and FGF23 in the Development of Left Ventricular
Hypertrophy in Chronic Kidney Disease
Chronic kidney disease (CKD) is a common condition affecting many Americans. FGF23 is a
hormone elevated in those with CKD to enhance the excretion of phosphate from the body.
However, the kidneys do not perform optimally in CKD, inhibiting the ability of FGF23 to
execute this function. Previous research indicates that high levels of FGF23 may play a role in
the development of left ventricular hypertrophy (LVH) in CKD. Still, additional factors, such as
hyperphosphatemia, may also contribute to LVH in CKD. This study aimed to remove phosphate
as a factor in LVH such that any change in heart size could be attributed to FGF23. As an animal
model of CKD, we used Juvenile cystic kidney disease (Jck) mice, which have progressively
reduced kidney function like someone with CKD. Jck mice were mated to GALNT3 knockout
mice, which have reduced FGF23, to generate four groups: GALNT3 mutant, Jck mutant, double
mutant, and phenotypically normal mice. From these four groups, the mice were split into two
groups: one with a normal (0.60%) phosphate diet and the other with a low (0.10%) phosphate
diet. The blood and hearts were collected from 12-14 week old mice. The Jck mutant and double
mutant mice exhibited elevated expression in common LVH gene markers. Serum analysis
indicated the restoration of inorganic phosphate to normal levels after reducing dietary phosphate
in GALNT3 and double mutant mice. Also, FGF23 levels declined in all mice on the low
phosphate diet. Despite these changes in serum phosphate and FGF23, the LVH markers in
mutant mice remained higher than normal mice. These data suggest that factors other than
FGF23 and hyperphosphatemia may contribute to development of LVH in CKD.