Stones: Evaluation, Prevention, and Non-Surgical Management
ROKS nomogram for predicting recurrent stone episodes, from Rule 2014
Evaluation after first stone episode, from Campbell's
Reasons to get a 24hr urine collection, from Campbell's
Stone management, from Campbell's
Risk factors
Epidemiology
- 1/11 (9%) people will make a stone (or more) in their lifetimes
- Risk factors: dry/hot climate, obesity, DM (increased uric acid levels, impaired ammonium excretion)
- After a stone episode, up to 50% will have another stone episode within 10yrs - metabolic syndrome (obesity, HTN, DM) increase stone forming risks
- ROKS nomogram: Created in 2014, predicts risk of stone formation based on patient and stone factors
Factors increasing stone formation
- Calcium: modulated by PTH and Vitamin D, produces both CaOx and CaPhos stones
- Sodium: increased levels get reabsorbed resulting in increased calcium secretion (Na/Ca exchanger)
- Oxalate: component of most common stone type (CaOx), only 20-50% come from diet, vitamin C (absorbic acid) is converted to oxalate
- Uric acid: can act as a nidus for CaOx stone formation, urine levels affected by pH + volume + uric acid quantity, precipitation affected more by urine acidity than uric acid concentration
- Matrix: noncrystalline material that forms nidus for stones
- Cysteine: disulfide bond results in insolube cystine
Factors decreasing stone formation
- Citrate: main stone inhibitor, complexes with calcium, inhibited by high acid foods (meat, cheese, eggs), fruit/veggies contain the most citrate and have lowest acid load
- Magnesium: complexes with oxalate, inhibits crystal growth
- Phosphate/pyrophosphate: complexes with oxalate, inhibits crystal growth
- Macromolecules: GAGs (chondroitin and heparin sulfate) and glycoproteins (Tamm-Horsfall and nephrocalcin) inhibit crystal aggregation
Anatomic risk factors
- UPJ obstruction: assocation questionable, as stone risk persists after treatment of obstruction
- Horseshoe kidney: 20% incidence, thought to be due to high ureteral insertion
- Caliceal diverticulum: combination of urinary stasis and stone forming factors
- Medullary stone kidney: unclear cause, combination of inability to acidify urine, hypercalcuria, hypocitraturia
Medication
- Increase stone risk factors: acetazolamide, topiramate, vitamin C, probenacid, antacids, chemotherapy
- Directly precipitate: triamterene, guafenesin, ephedrine, indinavir (radiolucent)
Stone Prevention
Dietary recommendations
- Drink more water: maintain UOP 2-3L to dilute salts and other stone forming agents, do not need to titrate to color
- Eat less salt: salt reabsorption in the tubule decreases calcium reabsorption, limit salt intake to < 2.3g daily (100mEq)
- Eat less meat: protein = amino acids -> high urinary acid load, all meat (mammal, bird, fish, etc) are equal, can also increase calcium excretion
- Oxalate-containing foods: only avoid if proven hyperoxaluria, likely due to enteric causes
- Vitamin C (absorbic acid): can be converted to oxalate, avoid high doses
Choosing fluids
- Volume is key - maintain UOP > 2.5L/d
- Water is best - dilutes urinary solutes
- Dark colas (contains phosphoric acid) are bad, and avoid other sugar-sweetened beverages
- Caffeinated drinks (coffee, tea) are fine
- Alcohol (wine, beer, etc) are fine
Juice options
- Citrus juice contains citric acid, which is converted to citrate and bicarbonate
- Grapefruit juice has the highest citrate level (197.5mEq/L)
- Grapefruit and orange juice both contain potassium in addition to citrate, but lemon juice does not
Calcium balance
- Decreased calcium intake leads to uninhibited oxalate gut absorption
- Calcium supplementation increases calcium stone risk
- Maintain normal calcium levels - 1000mg/d for women < 50 and men < 70, otherwise 1200mg/d
- Limit sodium to < 100mEq/d (sodium increases calcium retention)
Mineral Metabolism Workup
Patient history
- Personal/family history stones
- DM/obesity: insulin resistance impairs ammonium excretion, leading to low urine pH and uric acid stones
- Gout: causes hyperuricosuria
- HyperPTH: causes hypercalcemia and hypercalciuria
- Cancer, sarcoid, and granulomatous disease: increases risk for hypercalcemia through PTHrP or Vitamin D
- GI malabsorptions: increase risk for decreased calcium absorption (complexed to fats) and subsequent increased oxalate absorption (normally complexes with calcium and not absorbed)
Components
- Blood: electrolytes (BMP), Ca, Phos, Vit D, PTH (if hypercalcemia)
- UA: assess pH, urine crystals
- 24hr Urine (see next section)
- Stone analysis: to assess for unusual stone types
Hypercalciuria
- Resorptive: primary hyperPTH increases bone turnover and intestinal absorption, causing hypercalcemia and subsequent hypercalciuria, treated with parathyroidectomy
- Absorptive: increased GI tract absorption of calcium
- Renal: calcium wasting via nephron leakage
- Granulomatous disease: increased 1-alpha hydroxylase (produced by macrophages) -> increased Vitamin D production, treat with steroids
- Thiazide challenge: initiation of thiazide will lead to persistent hyperPTH if primary, but hyperPTH will resolve if secondary
- Overall, no need to differentiate between types besides diagnosing hyperPTH (does not change treatments)
24hr Urine Collection
Measured variables
- Volume: < 2-3L/d increases risk for mineral precipitation and stone formation
- Calcium: increased levels (> 200mg/d) lead to increased stone formation, no need to differentiate between the three types
- Oxalate: increased levels (> 40mg/d) complex with calcium and precipitate out, can be due to increased gut absorption
- Sodium: high urinary sodium (> 150mEq/d) leads to decreased proximal tubule sodium resorption causing decreased distal tubule calcium resorption
- Citrate: decreased levels (< 450-550mg/d) result from acidosis and increase calcium stone formation
- Magnesium: can bind oxalate, underlying cause for enteric hyperoxaluria can cause decreased magnesium absorption and subsequent decreased levels (< 80/d)
- Potassium: low levels (< 20-100mg/d)
- Uric Acid: increased levels (> 600-800mg/d) create nidus for CaOx crystallization, but main determinant for precipitation is pH, not uric acid level
- pH: low pH (< 5.5) induces uric acid precipitation, elevated levels increase CaPhos formation
- Sulfate: increased levels indicates high animal protein intake
- Creatinine: indicates adequacy of collection based on expected normal value for creatinine excretion (20-25mg/kg/d for men, 15-20mg/kg/d for women)
- Cystine: normal excretion 0.4% (cystinurics excrete 100%), saturated at 250mg/L, sodium nitroprusside turns purple in presence of cystine
Tips for Collection
- Make sure a day is chosen where urine can be completely collected
- Start after first morning void, and collect until morning void of following day
- Discontinue Vitamin D, calcium, antacids, diuretics, acetazolamide, and Vitamin C
Management based on metabolic workup parameters
| Dehydration | Hypercalcuria | Hypercalcemia | Hypernatruria | Hyperuricosuria | Low urinary pH | Hypocitraturia | Hyperoxaluria | Stone composition | Other findings | Management |
|---|---|---|---|---|---|---|---|---|---|---|
| Yes | - | Increase fluid intake to 2-3L | ||||||||
| No | Yes | Yes | No | - | CaPhos | HyperPTH | Parathyroidectomy | |||
| No | - | Thiazide diuretic | ||||||||
| Yes | Limit sodium intake | |||||||||
| No | Yes | Yes | - | Calcium | - | Hydration Alkalinization |
||||
| Uric acid | ||||||||||
| No | - | Hyperuricosemia | Treat underlying cause Allopurinol |
|||||||
| No | No | Yes | - | KCit supplement | ||||||
| No (increased) | - | CaPhos | Hypokalemia/Hypochloremia | KCit + Hydration (RTA I) | ||||||
| No | Yes | - | Limit dietary oxalate Consider B6 supplement |
|||||||
| No | Struvite | Urease-splitting bacteria | Complete stone removal Acetohydroxamic acid |
|||||||
| Cystine | Cystinuria | Hydration Alkalinization Thiola |
||||||||
| Ammonium acid urate | Radiolucent | Check for chronic diarrhea | ||||||||
| Xanthine | Check for mutation vs allopurinol use | |||||||||
| Calcium | Otherwise normal | KCit supplements | ||||||||
Medications
| Class | Mechanism | Indication | Side effects | Dosing |
|---|---|---|---|---|
| Thiazide diuretics | distal tubule calcium resorption, sodium excretion | Hypercalciuria, calcium stones | Hypokalemia (may need supplements), hyperuricosuria, hypercalcemia, hyperglycemia, hypocitraturia (secondary to intracellular acidosis), tachyphylaxis | HCTZ 25mg BID Chlorthalidone 25mg QD Indapamide 2.5mg QD |
| Potassium citrate (KCit) | Increases urinary citrate, alkalinizes urine, binds urinary calcium | Calcium stones, low urinary citrate, Type I RTA, chronic diarrhea (use liquid form), thiazide-induced hypocitraturia | GI symptoms, hyperK (requires regular monitoring), increased CaPhos risk, wax coating passes in stool | 20mg BID-TID |
| Calcium supplements | Prevents oxalate absorption, maintains normocalcemia | Hypocalcemia, hyperoxaluria - test on and off supplementation | Increases calcium stone risk | 500-600mg CaCarb BID |
| Sodium bicarbonate Sodium citrate |
Increases urinary citrate, alkalinizes urine | KCit replacement if hyperkalemia risk | Hypernatremia | |
| Allopurinol (Zyloprim) | Inhibits uric acid production | Calcium stones in setting of hyperuricosuria (> 800/day) and normal calcium, do not give for uric acid stones | Transaminitis, rash, myalgias | 300mg daily |
| Alpha-mercaptopropionylglycine (Thiola) | Inhibits formation of insoluble cystine bond | Cystinuria | Transaminitis, anemia, asthenia, GI distress, rash | 300mg BID, titrate up PRN |
| Acetohydroxamic acid | Urease inhibitor | Struvite stones that cannot be managed surgically | Phlebitis/DVT, hemolytic anemia (3-15%), hypercoagulable state, tremor, headache, rash, palpitations, GI distress, alopecia | 250mg BID-TID |
Sources:
- AUA Core Curriculum
- Miller, N. L., and M. S. Borofsky. "Evaluation and medical management of urinary lithiasis." Campbell-Walsh Urology. 12th ed. Philadelphia, PA: (2020).
- Pearle, M., J. Antonelli, and Y. Lotan. "Urinary Lithiasis: Etiology, Epidemiology, and Pathogenesis." Campbell-Walsh Urology. 12th ed. Philadelphia, PA: (2020).
- Pearle, Margaret S., et al. "Medical management of kidney stones: AUA guideline." The Journal of urology 192.2 (2014): 316-324.
- Rule, Andrew D., et al. "The ROKS nomogram for predicting a second symptomatic stone episode." Journal of the American Society of Nephrology 25.12 (2014): 2878-2886.