Does Idiopathic Hypercalciuria Trigger Calcium-Sensing Receptor–Mediated Protection from Urinary Supersaturation?

Abstract

Kidney stone formation is common, affecting 5 to 6% of the American adult population, and highly recurrent. Approximately 70% of stones are composed predominantly of calcium oxalate (CaOx) with small amounts of calcium phosphate (CaP); another 10% are largely CaP. The physicochemical requirement for stone formation is supersaturation of urine with respect to the stone minerals. In the case of calcium stones, supersaturation is driven by urine calcium concentration, which is a function of calcium excretion and urine volume. For CaP, supersaturation is also controlled by urine pH, because solubility of this salt decreases as urine pH rises; CaP stones are seen largely in patients with urine pH >6. Biopsies of renal medullary papillae of stone formers, taken during percutaneous nephrolithotomy, demonstrate that stone formers are also characterized by specific patterns of mineral deposition in tissue. Common idiopathic CaOx stone formers have interstitial deposits of CaP in the medullary interstitium, so-called Randall's plaques, which begin in the thin loops of Henle and extend downward toward the base of the papilla, where they can be seen beneath the urothelium.1 CaOx stones form as overgrowths on plaque, attached to the papillae.2 When the amount of plaque covering the papillary surface was quantified, it varied directly with urine calcium excretion and inversely with urine volume and pH.3 The factors that control urinary supersaturation also affect plaque formation, which seems to be critical to the initiation of most calcium stones. Medullary biopsy of patients with CaP stones have a different appearance. CaP deposits are found in the inner medullary collecting ducts and the terminal ducts of Bellini, associated with fibrosis and papillary deformity,4 and interstitial plaque abundance is low. The process of stone formation is less clear …