Kidney Week

Abstract: TH-PO565

TRPV5 Surface Expression Contributes to Glucose-Induced Hypercalciuria

Session Information

• Bone and Mineral Metabolism: Basic
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Menezes, Cameron J., University of Chicago, Chicago, Illinois, United States

Cameron J. Menezes,

• Bergsland, Kristin J., University of Chicago, Chicago, Illinois, United States

Kristin J. Bergsland,

• Worcester, Elaine M., University of Chicago, Chicago, Illinois, United States

Elaine M. Worcester,

• Coe, Fredric L., University of Chicago, Chicago, Illinois, United States

Fredric L. Coe,

• Ko, Benjamin S., University of Chicago, Chicago, Illinois, United States

Benjamin S. Ko,

Background

Lemann et al. showed that feeding normal (N) patients a glucose bolus increases fractional excretion of calcium (FECa). In addition, our group has shown that general feeding caused a significantly increased FECa of idiopathic hypercalciuric stone formers vs N patients. These observations imply a post prandial effect in calcium handling, with clinical implications for stone formers. We sought to identify transporter protein targets that mediate the effect of glucose induced hypercalciuria.

Methods

5 N women were placed on a low salt (65 mEq/d) diet for 3 days. Patients then fasted overnight, and reported to the Clinical Research Center for serial blood and urine collections for 5 hours, consuming 100 grams of glucose at 2 hours. Endogenous lithium clearance was measured to calculate distal delivery. Urine was filtered, spun and ultracentrifuged to isolate urinary exosomes from selected time points. Resulting samples were assayed by ELISA for transporter protein abundance of TRPV5. Student’s T-Tests were used to compare the last fasting period to periods of maximal change for metabolic parameters. A generalized linear model (GLM) was used to model the fractional excretion of distally delivered Ca (FEDCa).

Results

FECa rose with glucose feeding (p=0.02). Distal delivery of calcium did not differ significantly between the final fasting and any of the fed periods. FEDCa rose in parallel with FECa and rises significantly from the fasting period (p=0.015). TRPV5 expression decreased significantly after glucose feeding (p=0.047). A GLM (Table) with FEDCa as dependent, revealed TRPV5 and its known effector parathyroid hormone as significant predictors of FEDCa, with the overall model accounting for half the variation in FEDCa (R²=0.503).

Conclusion

We have recreated the hypercalciuric effect of glucose feeding, and have localized it to the distal nephron in a cohort of young women. The finding of reduced TRPV5 in urinary exosomes implies protein trafficking away from the apical membrane, and thus identifies TRPV5 as a key mediator of FEDCa in this setting.

Constant coefficient is in %. TRPV5 effect is in %/pmol/mg Cr. PTH effect is in %/pg/mL.

Funding

• NIDDK Support