Editing Stones: Epidemiology and Pathogenesis (section)

=== Hypercalcuria ===
* '''<span style="color:#ff0000">Most common abnormality identified in calcium stone formers</span>'''
** '''Recall, hypercalcuria is the most common cause of microscopic hematuria in children'''
* '''<span style="color:#ff0000">Classification:</span>'''
*# '''<span style="color:#ff0000">Absorptive hypercalcuria</span>'''
*#* '''Characterized by'''
*#*# '''Normal serum calcium'''
*#*# '''Normal or suppressed PTH'''
*#*# '''Hypercalcuria'''
*#** '''Increased intestinal absorption of calcium results''' '''in''' a transient increase in serum calcium, which suppresses serum PTH and results in increased renal filtration of calcium, ultimately leading to hypercalcuria.
*#** Serum calcium level remains normal because the increase in intestinal absorption of calcium is matched by enhanced renal calcium excretion
*#* '''Calcium fasting and load tests can discriminate between the various types of absorptive hypercalcuria'''; however, routine performance of these tests is not required
*#** '''Absorptive hypercalciuria type I: increased absorption will occur regardless of the amount of calcium in the diet'''. Therefore, these subjects will demonstrate an increased urinary excretion of calcium on both the fasting and the loading specimens.
*#** '''Absorptive hypercalciuria type II: normal amount of urinary calcium excretion during calcium restriction''', but will show elevations during their regular diet
*# '''<span style="color:#ff0000">Renal (leak) hypercalcuria</span>'''
*#* '''Characterized by'''
*#*# '''Normal serum calcium'''
*#*# '''Elevated PTH'''
*#*# '''High fasting urinary calcium levels'''
*#** '''Impaired renal reabsorption of calcium results in elevated urinary calcium levels leading to secondary hyperparathyroidism (elevated PTH).'''
*#*** '''Other causes of secondary hyperparathyroidism: rickets, osteopenia, CKD'''
*#*** Patients may have low or low/normal radial bone density due to secondary hyperparathyroidism
*#** Serum calcium levels remain normal because the renal loss of calcium is compensated by enhanced intestinal absorption of calcium and bone resorption as a result of increased secretion of PTH
*#** '''The elevated serum PTH and elevated fasting urinary calcium (except if absorptive hypercalciuria I) levels differentiate renal from absorptive hypercalciuria'''
*# '''<span style="color:#ff0000">Resorptive hypercalcuria</span>'''
*#* Infrequent abnormality; '''most commonly associated with primary hyperparathyroidism'''
*#* '''Characterized by:'''
*#*# '''Elevated serum calcium'''
*#*# '''Elevated PTH'''
*#*# '''Hypercalcuria'''
*#*# '''Hypophosphatemia'''
*#** '''Excessive PTH secretion from a parathyroid adenoma results in''' excessive bone resorption and increased renal synthesis of 1,25(OH)2D3, which in turn enhances intestinal absorption of calcium. The net effect is elevated serum and urine calcium levels and reduced serum phosphorus levels.
*#* '''Recurrent calcium phosphate (100%) brushite stones are unusual and should raise suspicion for primary hyperparathyroidism (resorptive hypercalciuria)'''
*#** Mechanism: elevated PTH increases phosphate excretion
*#* '''Additional, rare causes of resorptive hypercalciuria include hypercalcemia of malignancy, sarcoidosis''', '''thyrotoxicosis, and vitamin D toxicity'''. Many granulomatous diseases, including tuberculosis, histoplasmosis, leprosy, and silicosis, have been reported to produce hypercalcemia.
*#** The hypercalcemia in sarcoidosis is due to the production of 1,25(OH)2D3 from 1α-hydroxylase present in macrophages of the sarcoid granuloma
*# '''<span style="color:#ff0000">Idiopathic (unclassified) hypercalcuria</span>'''
*#* Often refers to unevaluated or unknown cause
*#* Patients may demonstrate hypercalcuria in all phases of the dietary calcium manipulation, but will not demonstrate serum abnormalities
*# '''<span style="color:#ff0000">Malignancy-associated hypercalemia</span>'''
*#* An assay for intact PTH can help distinguish patients with hyperparathyroidism from those with other causes of hypercalcuria. Tumours in patients with humoral hypercalcemia produce a PTH-related protein (PTHrP)
*# '''<span style="color:#ff0000">Glucocorticoid-induced hypercalemia</span>'''