Editing Stones: Diet and Pharmacologic 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 (2)'''
*#'''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.'''
*'''Drugs and dosages'''
**'''Hydrochlorothiazide (25mg orally, twice daily; 50mg orally, once daily)'''
**'''Chlorthalidone (25mg orally, once daily)'''
**Indapamide (2.5mg orally, once daily).
**Chlorthalidone (25-50 mg/day) or indapamide (2.5 mg/day) 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.
**'''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">Lassitude and sleepiness'''
***'''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'''
**'''Hypocitraturia'''
***'''Result of hypokalemia with intracellular acidosis'''
**'''Hypokalemia and hyperglycemia'''
***'''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
**'''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.'''