CUA GUIDELINE: EVALUATION & MEDICAL MANAGEMENT OF STONES 2016
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
- ALL patients
with upper urinary tract stones
- Includes:
- 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)
- Includes (6):
- 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: General dietary measures (Simple F***g Changes Prevent Calculi From Occurring)
- 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
- 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
- Moderate Vitamin C supplementation; >1000mg daily is not recommended due to the associated risk of hyperoxaluria and nephrolithiasis
- 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
- 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
- A diet high in Fiber, fruits, and vegetables may offer a small protective effect against stone formation
- 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)
- 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.