CUA: Evaluation and Medical Management of Stones (2016)

See Original CUA Guidelines

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

Diagnosis and Evaluation

• Limited metabolic evaluation
  • Includes:
    1. History and Physical Exam
    2. Laboratory (4)
       1. Urinalysis +/- culture
       2. Serum electrolytes (Na, K, Cl, HCO3)
       3. Serum calcium
       4. 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):
    1. Albumin
    2. Uric acid
    3. Parathyroid hormone (PTH) level IF serum calcium is high-high-normal (if PTH high and serum calcium high-high normal, consider primary hyperparathyroidism)
    4. 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)
    5. 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
    6. (CUA guidelines mention urinalysis again, and also separately mention urine pH and specific gravity, which should be included in urinalysis)
  • Indications (11):
    1. Children (<18 years of age)
    2. Bilateral or multiple stones
    3. Recurrent stones (having ≥2 kidney stone episodes in the past)
    4. Solitary (anatomical or functional) kidney
    5. Renal insufficiency
    6. Non-calcium stones (e.g. uric acid, cystine)
    7. Pure calcium phosphate stones
    8. Any stone requiring PCNL
    9. Any complicated stone episode that resulted in a severe (if even temporary) acute kidney injury, sepsis, or hospitalization
    10. 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.)
    11. 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

• General dietary measures (Simple F***g Changes Prevent Calculi From Occurring)
  1. Reduce Sodium intake to 1500mg daily (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
  2. Increase Fluid intake to 2.5-3L or a urine output of 2.5L; 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
  3. Moderate Vitamin C supplementation; >1000mg daily is not recommended due to the associated risk of hyperoxaluria and nephrolithiasis
  4. Reduce animal Protein and purine rich foods is suggested in patients with recurrent calcium oxalate and uric acid nephrolithiasis; protein intake increases urinary calcium, oxalate, and uric acid excretion
  5. Moderate dietary Calcium intake to 1000-1200mg/day; 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
  6. A diet high in Fiber, fruits, and vegetables may offer a small protective effect against stone formation
  7. Reduce Oxalate rich foods 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)
  1. Distal Renal tubular acidosis
  2. HyperCalciuria
  3. HyperPhosphaturia
  4. Chronic urinary tract Infection
  5. 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.