Description

• Stone formation within the urinary tract: Urinary crystals bind to form a nidus, which grows to form a calculus (stone).
• Range of symptoms: asymptomatic to obstructive; febrile morbidity if result of infection

Epidemiology

• Vesical calculosis (bladder stones) due to malnutrition during early life is frequent in the Middle East and in Asian countries.
• Incidence in industrialized countries seems to be increasing, probably due to improved diagnostics and increasingly rich diets.
• Increased incidence in patients with surgically induced absorption issues (IBD, gastric bypass)

Incidence

• In industrialized countries: 100 to 200/100,000 per year
• Predominant age: Mean age is 40 to 60 years.
• Predominant sex: male > female (~3:1)

Prevalence

• 10–15% in the United States
• Lifetime risk of >14% in men, >6% in women
  • Incidence is increasing in female, pediatric, and adolescent populations.

Etiology and Pathophysiology

• Supersaturation and dehydration lead to high salt content in urine which congregates.
• Stasis of urine
  • Renal malformation (e.g., horseshoe kidney, ureteropelvic junction obstruction)
  • Incomplete bladder emptying (e.g., neurogenic bladder, prostate enlargement, multiple sclerosis)
• Crystals may form in pure solutions (homogeneous) or on existing surfaces, such as other crystals or cellular debris (heterogeneous).
• Balance of promoters and inhibitors: organic (Tamm-Horsfall protein, glycosaminoglycan, uropontin, nephrocalcin) and inorganic (citrate, pyrophosphate)
• Calcium oxalate and/or phosphate stones (80%)
  • Hypercalciuria
    • Absorptive hypercalciuria: increased jejunal calcium absorption
    • Renal leak: increased calcium excretion from renal proximal tubule
    • Resorptive hypercalciuria: mild hyperparathyroidism
  • Hypercalcemia
    • Hyperparathyroidism
    • Sarcoidosis
    • Malignancy
    • Immobilization
    • Paget disease
• Hyperoxaluria
  • Enteric hyperoxaluria
    • Intestinal malabsorptive state associated with irritable bowel syndrome, celiac sprue, or intestinal resection
    • Bile salt malabsorption leads to formation of calcium soaps.
  • Primary hyperoxaluria: autosomal recessive, types I and II
  • Dietary hyperoxaluria: overindulgence in oxalate-rich food
• Hyperuricosuria
  • Seen in 10% of calcium stone formers
  • Caused by increased dietary purine intake, systemic acidosis, myeloproliferative diseases, gout, chemotherapy, Lesch-Nyhan syndrome
  • Thiazides, probenecid
• Hypocitraturia
  • Caused by acidosis: renal tubular acidosis, malabsorption, thiazides, enalapril, excessive dietary protein
• Uric acid stones (10–15%): hyperuricemia causes as discussed earlier
• Struvite stones (5–10%): infected urine with urease-producing organisms (most commonly Proteus sp.)
• Cystine stones (<1%): autosomal recessive disorder of renal tubular reabsorption of cystine
• Bladder stones: seen with chronic bladder catheterization and some medications (indinavir)
• In children: usually due to malnutrition

Genetics

• Up to 20% of patients have a family history. However, spouses of those who form stones have higher calcium excretion rates than controls, suggesting strong dietary–environmental factors.
• Autosomal dominant: idiopathic hypercalciuria
• Autosomal recessive
  • Cystinuria, Lesch-Nyhan syndrome, hyperoxaluria types I and II
  • Ehlers-Danlos syndrome, Marfan syndrome, Wilson disease, familial renal tubular acidosis

Risk Factors

• White > Asian > African American
• Male
• Family history (increases risk by up to 2.5 times)
• Diet rich in protein, refined carbohydrates, and sodium; carbonated drinks; low calcium diet; low fluid intake
• Occupations associated with a sedentary lifestyle or with a hot, dry workplace
• Incidence rates peak during summer secondary to dehydration, hot climates.
• Obesity
• Surgically/medically induced malabsorption (Crohn disease, gastric bypass, celiac, primary hyperparathyroidism)
• Horseshoe kidney (incidence of 21–60%)
• Medications that can increase risk of forming calcium and uric acid stones
• Recent literature suggesting possible association between microbiome (gut and urinary) and urolithiasis

General Prevention

• Hydration (1)
• Decrease salt and meat intake.
• Avoid oxalate-rich foods.

Pediatric Considerations

• Increasing in prevalence due to obesity, diabetes, and hypertension
• Additional risk factor considerations include renal disease or immaturity, preterm birth, and low birth weight.
• Ultrasound should be considered in children before CT imaging to reduce radiation exposure.
• Consider additional work-up to evaluate for metabolic abnormality or hereditary etiology.
• Children with uncomplicated ureteral stones of ≤10 mm can be offered observation with or without medical expulsion therapy (MET) using α-blockers.

Pregnancy Considerations

• Pregnant women have the same incidence of renal colic as do nonpregnant women.
• Most symptomatic stones occur during the 2nd and 3rd trimesters, heralded by symptoms of flank pain/hematuria.
• Most common differential diagnosis is physiologic hydronephrosis of pregnancy. Use ultrasound to avoid irradiation. Noncontrast-enhanced CT scan also is diagnostic.
• 30% require intervention, such as stent placement.
• Pregnant women who have ureteral stones with symptoms that are generally well controlled should be offered observation as first-line therapy.