Thien Phan
Texas A&M University School of Medicine
Bryan, TX
Impact of lymphangiogenesis on renal phosphate handling following kidney injury
Thien Phan and Joseph M. Rutkowski
Overconsumption of inorganic phosphate (Pi) increases renal dysfunction, tubular cell damage, and vascular calcification, hallmarks of kidney disease. Conversely, acute kidney injury (AKI) and chronic kidney disease (CKD) result in Pi retention and hyperphosphatemia. We hypothesized that the damage caused by chronic Pi consumption likely induces renal lymphangiogenesis and that manipulating lymphatic density may alter renal Pi (and, by extension, calcium) handling. We first identified significantly increased expression of VEGF-C/D and lymphangiogenesis in kidneys of mice consuming a 2% Pi diet for 3 weeks or 2 months by immunofluorescence. We then utilized “KidVD” mice, a mouse model of kidney-specific inducible expression of potently lymphangiogenic VEGF-D to expand lymphatic density and test Pi handling. Measures of Pi and Ca2+ handling were normal in KidVD mice compared to their littermates during 3 weeks of 2% Pi diet, suggesting that lymphatics alone do not impact this mineral axis. In a Pi-driven CKD model, mice were injured with a single 10 mg/kg cisplatin dose and allowed to recover for 2 weeks. Mice were then placed on either chow or 2% Pi diet for 3 weeks with VEGF-D induction. AKI led to Pi retention in all mice. Female KidVD mice demonstrated similar Pi handling to controls, but significantly increased Ca2+ excretion. All male mice demonstrated a more pronounced injury response by eGFR. Male KidVD mice, however, demonstrated significantly increased Pi excretion compared to controls. Renal lymphangiogenesis thus appears to decrease Pi retention following AKI, potentially aiding in the recovery response.
SACNAS National Diversity in STEM Conference, Portland, OR, October 26-28, 2023
