Editing Stones: Evaluation and Medical Management (section)

===Calcium or calcium phosphate stones===

==== <span style="color:#ff0000">Thiazide diuretics</span> ====

*'''<span style="color:#ff0000">Indications</span>'''
**'''<span style="color:#ff0000">Should be offered to patients with (2):</span>'''
***'''<span style="color:#ff0000">Hypercalcuria AND</span>'''
***'''<span style="color:#ff0000">Recurrent calcium or calcium phosphate stones</span>'''
* '''Mechanism of Action'''
*# '''Directly stimulate calcium reabsorption in the distal nephron''' (hypocalcuric effect)
*# '''Promotes excretion of sodium causing extracellular volume depletion'''
*#* '''Long-term thiazide therapy results in volume depletion, extracellular volume contraction, and proximal tubular resorption of sodium and calcium.'''
* '''<span style="color:#ff0000">Drugs and dosages'''
*#'''<span style="color:#ff0000">Hydrochlorothiazide</span> (50mg orally, once daily;''' 25mg orally, twice daily''')'''
*#'''<span style="color:#ff0000">Chlorthalidone</span>''' (25mg orally, once daily)
*#'''<span style="color:#ff0000">Indapamide</span> (2.5mg orally, once daily)'''
*#*Chlorthalidone or indapamide are preferred to hydrochlorothiazide since they are long-acting and are once a day dosing.
*#* Indapamide is technically not a thiazide but does share a successful hypocalciuric effect with the other agents.
* '''<span style="color:#ff0000">Patients placed on thiazide diuretics for management of hypercalciuria should also be placed on dietary sodium restriction'''
** '''An excess sodium load will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria.'''
* '''<span style="color:#ff0000">Adverse events'''
** '''<span style="color:#ff0000">Sleepiness and lassitude'''
*** '''<span style="color:#ff0000">Most common side effects of thiazides'''
*** Can occur in the absence of hypokalemia
*** Usually seen on initiation of treatment but resolves with continued therapy.
** '''<span style="color:#ff0000">Metabolic/electrolyte abnormalities''' ('''3 hypers, 3 hypos + metabolic alkalosis''')
**# '''<span style="color:#ff0000">Hyperglycemia'''
**# '''<span style="color:#ff0000">Hyperlipidemia'''
**# '''<span style="color:#ff0000">Hyperuricemia'''
**# '''<span style="color:#ff0000">Hypokalemia'''
**# '''<span style="color:#ff0000">Hypomagnesemia'''
**# '''<span style="color:#ff0000">Hypocitraturia'''
**# '''<span style="color:#ff0000">Metabolic alkalosis'''
**'''<span style="color:#ff0000">Hypokalemia and glucose intolerance'''
*** '''The degree of diuretic-induced hypokalemia correlates with level of hyperglycemia.'''
**** Mechanism: hypokalemia impairs insulin secretion, thereby increasing plasma glucose.
***'''<span style="color:#ff0000">Potassium supplementation (either potassium citrate or potassium chloride)</span>''' 
****'''<span style="color:#ff0000">May be needed when thiazide therapy is employed because of the hypokalemic effects of these medications</span>'''
****'''<span style="color:#ff0000">Should always be considered at either the onset of thiazide therapy or upon the discovery of glucose intolerance'''
***** '''Can prevent or significantly lessens the degree of hypokalemia or glucose intolerance'''
***** '''Can be administered as potassium citrate or with dietary supplements such as a banana per day'''
****** '''Citrates are generally well tolerated, with only a small risk for GI upset'''
******* A liquid preparation of potassium citrate, rather than the slow-release tablet preparation, is recommended in patients with rapid intestinal transit time (i.e. chronic diarrhea); the slow-release medication may be poorly absorbed
****** Conflicting evidence of an increased risk of calcium phosphate stone formation with the long-term use of potassium citrate therapy
***** Particularly important in patients with evident potassium deficiency, patients on digitalis therapy, and those individuals who develop hypocitraturia
****'''The addition of amiloride or spironolactone may avoid the need for potassium supplementation'''.
****Triamterene, although it is potassium-sparing, should be avoided as stones of this compound have been reported
**'''Hypocitraturia'''
***'''Result of hypokalemia with intracellular acidosis'''
**'''Patients with undiagnosed primary hyperparathyroidism may develop hypercalcemia after initiation of thiazide therapy'''
*** Although most patients with primary hyperparathyroidism demonstrate hypercalcemia and hypercalciuria, a normal serum calcium level in the presence of an inappropriately high serum PTH value may be seen in some cases, making the diagnosis more difficult. Administration of a thiazide diuretic will enhance renal calcium reabsorption and exacerbate the hypercalcemia, thereby facilitating the diagnosis (“thiazide challenge”)
**** In the thiazide challenge, cessation of thiazide should reduce PTH and serum calcium. However, in primary hyperparathyroidism, PTH and serum calcium remain persistently elevated with cessation of thiazide.
** '''Bisphosphonates combined with thiazide diuretics appear to reduce hypercalciuria while protecting the bone'''
* '''Thiazide diuretics lose their effectiveness in the treatment of hypercalciuria in up to 25% of patients on long-term management.'''
** '''Loss of effectiveness is due to increased serum calcium levels which stimulate the C cells in the thyroid to produce more calcitonin.''' Increased calcitonin leads to increased urinary calcium excretion.

==== <span style="color:#ff0000">Potassium citrate</span> ====
*'''<span style="color:#ff0000">Indications</span>'''
**'''<span style="color:#ff0000">Should be offered to patients with (2)</span>'''
**#'''<span style="color:#ff0000">Hypocitraturia AND</span>'''
**#'''<span style="color:#ff0000">Recurrent calcium or calcium phosphate stones</span>'''
**#*'''Citrates are first-line therapy for the management of RTA, thiazide-induced hypocitraturia, and idiopathic hypocitraturia'''
**#** Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia found in patients with distal RTA
**#*'''Calcium stone-forming patients with normal citrate excretion but low urinary pH may also benefit from citrate therapy'''
**#**There is also a risk that higher urine pH can promote calcium phosphate stone formation, or change calcium oxalate stone formers to calcium phosphate stone formers.
**#* '''Potassium citrate is preferred over sodium citrate'''
**#**'''Patient's treated with sodium alkali will occasionally begin forming calcium oxalate stones due to an excess sodium load that will inhibit reabsorption of calcium in the proximal tubule, thereby causing hypercalciuria'''
**#**'''If the patient is at risk for hyperkalemia, other agents such as sodium bicarbonate or sodium citrate should be considered.'''
*'''<span style="color:#ff0000">Adverse Events (2)</span>'''
**'''<span style="color:#ff0000">Hyperkalemia</span>'''
**'''<span style="color:#ff0000">GI upset</span>'''