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Abstract: PO0327

Heterogeneity of Mechanisms for Idiopathic Hypercalciuria in Calcium Stone Formers

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Helding, George Andrew, University of Chicago, Chicago, Illinois, United States
  • Worcester, Elaine M., University of Chicago, Chicago, Illinois, United States
  • Bergsland, Kristin J., University of Chicago, Chicago, Illinois, United States
  • Coe, Fredric L., University of Chicago, Chicago, Illinois, United States
Background

In past research, we have found evidence that patterns of segmental nephron tubule calcium reabsorption differ between the sexes in calcium (Ca) stone formers (SF) demonstrating a different underlying mechanism of their hypercalciuria. Whether or not these mechanisms differ between calcium oxalate (CaOx) and calcium phosphate (CaP) SF is not known.

Methods

We studied 18 CaOx subjects (12 male), 17 CaP subjects (9 male), and 25 normal (N) subjects (13 male) in both the fasted and fed state. Subjects ate a diet consisting of three isocaloric meals with hourly blood and urine samples for 14 hours. We measured endogenous lithium clearance to assess proximal tubule (PT) sodium reabsorption. To account for within-subject correlation due to repeated measures, generalized estimating equations (GEE) were used to estimate and test mean laboratory values between groups. Linear mixed effects models were used to model urine Ca, distally delivered Ca, absolute reabsorption of distally delivered Ca, and the urine-plasma lithium ratio.

Results

In SF women, distal Ca reabsorption is decreased compared to N women, while in SF men, PT Ca reabsorption is significantly decreased with a more modest reduction in distal Ca reabsorption compared to normal men. Among female CaP SF we found an abnormally high response of urine Ca to PTH that appears to affect post PT Ca reabsorption. Among female CaP and CaOx SF and male CaOx SF we found a clear difference of urine Ca response to ultrafiltrate Ca concentration. This difference was absent in male CaP SF who had a unique increase in the dependence of distal Ca delivery on lithium reabsorption in the PT. CaOx male SF also had other PT abnormalities such as modeled urine Ca that was abnormally dependent on the urine-plasma lithium ratio. In addition, CaOx male SF had modeled lithium reabsorption that was abnormally responsive to both urine sodium, an ECF volume marker, and UF Ca concentration, presumably mediated through the cell surface Ca receptor (CaSR).

Conclusion

CaP and CaOx SF have differing abnormalities of Ca handling as compared to their same sex normals. In particular, phenotype specific abnormalities related to the CaSR exist in CaOx men and abnormalities related to the PTH receptor exist in CaP women.

Funding

  • NIDDK Support