Editing CUA: Evaluation and Medical Management of Stones (2016)

'''See [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234401/ Original CUA Guidelines]'''

'''See 2019 AUA Guideline Notes on Evaluation and Medical Management of Stones'''

== Diagnosis and Evaluation ==

* '''Limited metabolic evaluation'''
** '''Includes:'''
**# '''History and Physical Exam'''
**# '''Laboratory (4)'''
**## '''Urinalysis +/- culture'''
**## '''Serum electrolytes (Na, K, Cl, HCO3)'''
**## '''Serum calcium'''
**## '''Serum creatinine'''
**#* '''Same as AUA except AUA includes serum uric acid as part of limited metabolic evaluation'''
** '''Indications:'''
*** '''ALL patients''' with upper urinary tract stones
**** '''Even the first-time stone-former''', without any identifiable risk factors for recurrent stone formation, should undergo a limited metabolic evaluation to rule out potential systemic disorders, such as hyperparathyroidism and renal dysfunction
* '''In-depth metabolic evaluation'''
** '''Includes (6):'''
**# '''Albumin'''
**# '''Uric acid'''
**# '''Parathyroid hormone (PTH) level IF serum calcium is high-high-normal''' (if PTH high and serum calcium high-high normal, consider primary hyperparathyroidism)
**# '''Vitamin D, IF low normal serum calcium''' (in low normal serum calcium, PTH will increase and therefore increase Vitamin D levels; if vitamin D low then consider vitamin D deficiency)) '''or elevated serum PTH''' (vitamin D deficiency may be cause of secondary primary hyperparathyroidism)
**# '''Two 24-hour urine collections assessing (9): volume, creatinine, sodium, potassium, calcium, magnesium, oxalate, uric acid, and citrate;'''
**#* '''Cystine can be assessed in suspected or confirmed cystine stone'''
**# ('''CUA guidelines mention urinalysis again''', and also separately mention '''urine pH and specific gravity''', which should be included in urinalysis)
** '''Indications (11):'''
**# '''Children (<18 years of age)'''
**# '''Bilateral or multiple stones'''
**# '''Recurrent stones (having ≥2 kidney stone episodes in the past)'''
**# '''Solitary (anatomical or functional) kidney'''
**# '''Renal insufficiency'''
**# '''Non-calcium stones (e.g. uric acid, cystine)'''
**# '''Pure calcium phosphate stones'''
**# '''Any stone requiring PCNL'''
**# '''Any complicated stone episode that resulted in a severe (if even temporary) acute kidney injury, sepsis, or hospitalization'''
**# '''History of kidney stones and systemic disease that increases the risk of kidney stones (e.g. gout, osteoporosis, bowel disorders, hyperparathyroidism, renal tubular acidosis, etc.)'''
**# '''Occupation where public safety is at risk (e.g. pilots, air traffic controller, police officer, military personnel, firemen)'''
*** '''May also be considered for''' '''any patient who is interested and willing to participate''' in the endeavor and is willing to alter his/her diet or begin pharmacotherapy
* '''Struvite stones'''
** '''Routine metabolic evaluation is not usually recommended''' due to the infectious nature and cause of struvite stones; '''however, routine urine culture and radiological investigations are necessary in these patients'''
* '''All kidney stones should be submitted for analysis'''

== Management ==

=== First-line ===

* '''<span style="color:#ff0000">General dietary measures (</span><span style="color:#0000ff">S</span><span style="color:#ff0000">imple </span><span style="color:#0000ff">F</span><span style="color:#ff0000"><span style="color:#ff0000">***g </span><span style="color:#0000ff">C</span><span style="color:#ff0000">hanges </span><span style="color:#0000ff">P</span><span style="color:#ff0000">revent </span><span style="color:#0000ff">C</span><span style="color:#ff0000">alculi </span><span style="color:#0000ff">F</span><span style="color:#ff0000">rom </span><span style="color:#0000ff">O</span><span style="color:#ff0000">ccurring</span>)'''
*# '''<span style="color:#ff0000">Reduce </span><span style="color:#0000ff">S</span><span style="color:#ff0000">odium intake to 1500mg daily</span>''' (not exceed 2300mg daily) '''is recommended in patients with recurrent calcium nephrolithiasis'''; '''increased salt intake is associated with hypercalcuria;''' RCTs have demonstrated a benefit of dietary sodium restriction
*# '''<span style="color:#ff0000">Increase </span><span style="color:#0000ff">F</span><span style="color:#ff0000">luid intake to 2.5-3L or a urine output of 2.5L;</span>''' most evidence suggests that it is not the type of fluid ingested that is important for stone prevention but rather the absolute amount of fluid volume taken in per day
*# '''<span style="color:#ff0000">Moderate Vitamin </span><span style="color:#0000ff">C</span><span style="color:#ff0000"> supplementation; >1000mg daily is not recommended due to the associated risk of hyperoxaluria</span>)''' and nephrolithiasis
*# '''<span style="color:#ff0000">Reduce animal </span><span style="color:#0000ff">P</span><span style="color:#ff0000">rotein and purine rich foods</span> is suggested in patients with recurrent calcium oxalate and uric acid nephrolithiasis; protein intake increases urinary calcium, oxalate, and uric acid excretion'''
*# '''<span style="color:#ff0000">Moderate dietary </span><span style="color:#0000ff">C</span><span style="color:#ff0000">alcium intake to 1000-1200mg/day</span>'''; should calcium supplementation be required in a patient with calcium oxalate stone disease, '''calcium supplementation should be taken at mealtimes'''; '''reduced calcium intake increases risk of stone disease due to increased oxalate absorption''' since oxalate normally binds to calcium for excretion
*# '''<span style="color:#ff0000">Diet high in </span><span style="color:#0000ff">F</span><span style="color:#ff0000">iber, fruits, and vegetables</span>''' may offer a small protective effect against stone formation
*# '''<span style="color:#ff0000">Reduce </span><span style="color:#0000ff">O</span><span style="color:#ff0000">xalate rich foods</span> such as (Oxalate Rich Chocolate, Pepper, Nuts) Okra, Rhubarb, Chocolate, Pepper, Nuts, spinach, beets, and tea'''
** '''In calcium oxalate stone-formers with documented vitamin D deficiency, repletion is appropriate, but monitoring for hypercalcuria on 24-hour urine in follow-up is suggested'''
** '''Only excessive intake of dairy products (>4 servings/day) leads to greater urinary calcium excretion. Changes in dietary fat intake do not alter urine calcium excretion'''

=== Second-line ===
'''Specific prophylaxis based on stone composition'''

==== Calcium oxalate or mixed calcium oxalate/calcium phosphate stones ====

* '''See Figure 1 from Original CUA Guideline'''
* '''Hypercalcuria - Thiazides'''
** '''Thiazides decrease urinary calcium and decrease stone''' '''recurrence in patients with recurrent calcium stones with and without metabolic abnormalities'''
** '''Chlorthalidone (25 mg/day) or indapamide (2.5 mg/day) are preferred to hydrochlorothiazide (25 mg orally BID; 50 mg orally daily) since they are long-acting and are once a day dosing.'''
** '''The dose-dependent side effects of thiazide diuretics include (6, 3 hypos, 3 hypers): hypokalemia, hyperglycemia, hyperlipidemia, hypocitraturia, hypomagnesemia, and hyperuricemia with metabolic alkalosis'''
** '''Combining thiazide diuretics with potassium citrate or potassium chloride prevents hypokalemia and hypochloremic metabolic alkalosis'''
* '''Hypocitraturia - Alkali citrate'''
** '''Alkali citrate (potassium citrate, potassium magnesium citrate, sodium citrate, etc.) results in a significant increase in urinary pH and urinary citrate and decreases recurrent nephrolithiasis.'''
*** Overall, potassium citrate is preferred over sodium citrate, as the sodium load may increase urinary calcium excretion.
** '''Potassium citrate'''
*** Most commonly studied agent
*** '''Dosages range from 30‒60 mEq in divided doses daily'''
*** '''Gastrointestinal upset is the primary side effect'''
*** '''Hyperkalemia may occur in patients with renal insufficiency. In this situation, treatment with sodium-based alkali''' (sodium citrate, sodium bicarbonate) '''is an alternative'''
** '''Careful monitoring of urine pH is recommended given the risk of calcium phosphate stone formation with the long-term use of potassium citrate therapy'''
* '''Hyperuricosuria - Allopurinol'''
** '''In patients with calcium oxalate stones with hyperuricosuria and normocalciuria, allopurinol reduces stone recurrence. Allopurinol is not effective in reducing stone recurrence in patients with normal urinary uric acid levels'''
** '''Allopurinol blocks the ability of xanthine oxidase to convert xanthine to uric acid. This decreases serum uric acid which decreases urinary uric acid.'''
** Typical allopurinol dosage is 200‒300 mg daily in single or divided doses.
** Major side effects include rash, GI upset, abnormal liver enzyme levels, and prolonged elimination in renal disease
* '''Hyperoxaluria – limit oxalate intake'''
** '''If limiting oxalate intake and moderating calcium is insufficient, consider vitamin B6'''

==== Uric acid stones ====

* '''See Figure 2 from Original CUA Guideline'''
* '''May form as the result of underlying metabolic disorders, including gout, diabetes, obesity, metabolic syndrome, excessive bicarbonate loss due to high output bowel disease, myeloproliferative disorders, and tumour lysis syndrome'''
* '''Most commonly associated with low urinary pH (most important) and low urine volume rather than hyperuricosuria'''
* '''Focus of treatment is to correct urine pH > 5.5 (target 6.5) with the use of alkali citrate and increase urine volume''' rather than institute treatment of uric acid production
* '''Allopurinol may be used as adjunctive therapy in patients with hyperuricemia or hyperuricosuria'''

==== Pure calcium phosphate stones ====

* '''See Table 1 from Original CUA Guideline'''
* '''Conditions associated with calcium phosphate stones (5): (Dr. Cal PhIP)'''
*# '''Distal Renal tubular acidosis'''
*# '''HyperCalciuria'''
*# '''HyperPhosphaturia'''
*# '''Chronic urinary tract Infection'''
*# '''Primary hyperParathyroidism'''
* '''Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia found in patients with distal renal tubular acidosis and reduces risk of stone formation'''

==== Cystine stones ====

* Cystinuria is a common genetic disorder affecting 1/7000 individuals
* Cystine stone-formers often present in childhood or as teenagers
* '''Patients with cystinuria should be encouraged to maintain a urine output ≥3 L daily''' (often demanding oral intake of 3.5–4 L of fluid). '''Sodium and protein restriction are also recommended'''
* '''Urinary alkalinisation with potassium citrate is the initial step in medical therapy, with the goal of achieving a urine pH > 7.0.'''
** The solubility of cystine increases significantly between a urine pH of 7.0-7.5.
** '''A urinary pH > 7.5, however, should be avoided, as this may promote calcium phosphate stone formation.'''
* '''Acetazolamide may be used as an adjunct to urinary alkalinization when potassium citrate alone is ineffective'''
* '''If alkalizing agents fail to adequately control cystine stone formation, thiol binding agents, such as tiopronin (α-mercaptopropionylglycine)''' 800‒1200mg '''or penicillamine''' 1‒2 g in daily divided doses, '''may be used'''
** '''Side effects from penicillamine can be significant''' and include fever, arthralgias, rash, dysgeusia, leucopenia, and proteinuria
** '''Tiopronin''' is not currently available in Canada
** '''Captopril''' '''is not currently recommended for cystine stone prevention'''
* '''See Figure 3 from Original CUA Guideline'''

==== Struvite stones ====

* '''Surgical removal of stone material is the standard therapy'''.
* Whenever possible, foreign bodies, such as urinary stents or catheters, should be removed.
* '''The urease inhibitor acetohydroxamic acid (AHA) has been studied with limited success and not insignificant side effects.''' This agent is not currently available in Canada.
* '''A better-tolerated prevention strategy may be low-dose suppressive antibiotic therapy''', but the risk of bacterial resistance should be taken into consideration.