Table 2.

Conditions impacting the CaSR in the kidney

Type of Condition	Name	Biological Effects
1. Genetic diseases with CaSR dysfunction in all CaSR-expressing tissues	FHH, NHPT, and NSHPT ADH Bartter syndrome type V with activating CaSR mutations	↓Sensitivity to Cao2+ with relative or absolute hypocalciuria ↑Sensitivity to Cao2+ with relative or absolute hypercalciuria Hypokalemia, hyperreninemia, and hyperaldosteronism
2. Polymorphisms in the CaSR gene*	Glycine at codon 990 in CaSR C tail 986A, 990C, and 1011G haplotype	Apparent receptor activation. Hypercalciuria, ↓PTH levels, and ↑PTH suppressibility in patients with renal failure and 2o HPT Greater risk of stones in PHPT
3. Acquired disorders with CaSR dysfunction in multiple tissues	Inactivating autoantibodies to the CaSR (AHH) Activating autoantibodies to the CaSR†	↓Sensitivity to Cao2+ with relative or absolute hypocalciuria ↑Sensitivity to Cao2+ with relative or absolute hypocalciuria
4. Primary renal dysfunction impacting the CaSR in the kidney	Renal insufficiency	Reduced CaSR expression‡ and hypocalciuria
5. Modulation of CaSR by endogenous ligands	Hypercalcemia	Urinary concentrating defect, hypercalciuria, and ↓1,25(OH)2D3§ synthesis.

FHH, familial hypocalciuric hypercalcemia; NHPT, neonatal hyperparathyroidism; NSHPT, neonatal severe primary hyperparathyroidism; ADH, autosomal dominant hypoparathyroidism; AHH, autoimmune hypocalciuric hypercalcemia; Ca_o²⁺, extracellular calcium; HPT, hyperparathyroidism; PHPT, primary HPT;

^*For additional examples of the impact of polymorphisms on CaSR function, see text.

^†Impact on renal calcium handling not known.

^‡Level of expression determined in rats with experimental renal insufficiency, not known in human renal disease.

^§Decrease in 1,25(OH)₂D₃ probably results indirectly from CaSR inhibition of PTH secretion as well as through direct inhibition of 1-hydroxylase by CaSR in proximal tubule.