Nephrolithiasis

Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis presents with colicky flank pain, which radiates to the groin, and hematuria due to damage to the ureters. Diagnosis is made by noncontrast CT of the abdomen and pelvis or by renal ultrasound, and urinalysis is performed to exclude concomitant urinary tract infection (UTI). Management depends on the size of the stone. Small stones likely to pass on their own are managed conservatively with hydration and analgesics. Large stones unlikely to pass spontaneously are managed with extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy, or percutaneous nephrolithotomy. Nephrolithiasis can be complicated by hydronephrosis or acute pyelonephritis. Adequate hydration is the best prophylactic intervention to prevent kidney stones.

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Overview

Definition

Nephrolithiasis (also known as kidney stones, urolithiasis, or urinary calculi) is the formation of stones anywhere along the urinary tract.

Classification

There are 5 main types of kidney stones:

  • Calcium oxalate stone: 
    • Accounts for 75% of all kidney stones (most common type)
    • Envelope or dumbbell-shaped crystals
  • Uric acid stone:
    • Accounts for 10% of all kidney stones
    • Rhomboid or rosette-shaped crystals
  • Struvite (ammonium magnesium phosphate) stone: 
    • Accounts for 5%–10% of all kidney stones
    • Coffin-lid–shaped crystals
  • Calcium phosphate stone:
    • Accounts for 5% of all kidney stones
    • Wedge-shaped prism
  • Cystine stone:
    • Accounts for < 5% of kidney stones
    • Hexagonal crystals
    • Mnemonic: Pronounce cystine stones as “sixtine” stones (six-sided stones) to remember their shape.

Epidemiology

  • More common in men than women
  • Most common in white, non-Hispanic men
  • Peak incidence: 45–70 years old, but can occur at any age
  • Prevalence increases with age.

Etiology

Normally soluble material supersaturates the urine and crystal formation begins.

Risk factors:

  • Family history
  • Medical conditions:
    • Urinary tract infections (UTIs)
    • Cystinuria
    • Gout (high uric acid)
    • Hyperparathyroidism (high calcium levels)
    • Hypertension
    • Diabetes
    • Inflammatory bowel disease (IBD)
    • Short gut syndrome
  • Diet:
    • High sodium: decreased sodium and calcium reabsorption in the proximal tubule → hypercalciuria
    • High calcium
  • Dehydration: causes an excessive concentration of urine solutes → stone formation
  • Loop diuretics: inhibits calcium reabsorption → hypercalciuria

Pathophysiology

Calcium oxalate stones

  • Idiopathic normocalcemic hypercalciuria (most common cause)
  • Ethylene glycol (antifreeze) ingestion: 
    • Ethylene glycol is metabolized to oxalate by alcohol dehydrogenase and aldehyde dehydrogenase.
    • Oxalate filtered in the urine binds to urinary calcium producing calcium oxalate crystals.
  • Decreased urine pH:
    • Excessive H+ ions bind to citrate, resulting in hypocitraturia.
    • Urinary calcium can no longer bind to citrate and binds to oxalate instead, producing calcium oxalate crystals. 
  • Excessive vitamin C (ascorbic acid) ingestion: decreases urine pH resulting in calcium oxalate crystals
  • Crohn’s disease or small bowel resection:
    • Decreased absorption of fat due to damaged mucosa (Crohn’s disease) or small surface area (small bowel resection)
    • Calcium in the GI lumen binds to fat, resulting in increased free oxalate absorption from the GI tract. 
    • Oxalate filtered across the glomeruli binds to urinary calcium, producing calcium oxalate crystals. 

Uric acid stones

  • Decreased urine pH:
    • Excessive H+ binds to urate and forms uric acid.
    • Uric acid moieties coalesce to form uric acid crystals.
  • Arid climate:
    • Excessive sweating causes volume depletion.
    • Volume depletion concentrates urine, allowing uric acid moieties to coalesce and form crystals.
  • Hyperuricemia: Uric acid crystals are formed by an increase in filtered uric acid.
  • Increased cell turnover (e.g., lymphoma, leukemia):
    • Purine breakdown in the cell nucleus produces uric acid.
    • Excessive uric acid is filtered across glomeruli and forms uric acid crystals.

Struvite stones

  • UTI with urease-positive bacteria
  • Urease breaks down urea into ammonia and CO2.
  • Ammonia binds to magnesium and phosphate forming struvite stones.
  • Commonly implicated bacteria:
    • Staphylococcus saprophyticus
    • Klebsiella pneumoniae
    • Proteus mirabilis

Calcium phosphate stones

  • Increased urine pH results in high levels of monohydrogen phosphate anions.
  • Monohydrogen phosphate binds to calcium-forming calcium phosphate crystals.

Cystine stones

  • Cystinuria: autosomal recessive defect in sodium-dibasic amino acid cotransporter
  • Results in decreased tubular reabsorption of cystine, ornithine, arginine, and lysine
  • Cystine moieties are retained in the urine, coalesce, and form cystine stones.

Overview

Table: Pathophysiology of kidney stones
Type of stone%CausesCrystalsUrine pH
Calcium oxalate75%
  • Hypercalciuria
  • Ethylene glycol ingestion
  • Excessive vitamin C ingestion
  • Crohn’s disease
  • Small bowel resection
Envelope or dumbbell shaped
Uric acid10%
  • Arid climate/excessive sweating
  • Hyperuricemia (e.g., gout)
  • Increased cell turnover
Rhomboid or rosette shaped
Struvite (ammonium magnesium phosphate)5%–10%UTI with urease-positive bacteriaCoffin-lid shaped
Calcium phosphate5%Increased urine pHWedge-shaped prism
Cystine< 5%CystinuriaHexagonal

Sites of obstruction and complications

  • Kidney stones can lodge into any of the 3 natural narrowings along the ureter:
    • Ureteropelvic junction (junction of the renal pelvis and ureter)
    • Ureter at the pelvic inlet (site of ureteral crossing of the iliac vessels)
    • Ureterovesical junction (junction of the ureter and urinary bladder) 
  • A stone lodged at any of the 3 locations can cause obstruction and consequent proximal complications: 
    • Acute pyelonephritis
      • Obstruction of the urinary tract, which allows for proximal overgrowth of bacteria
      • Inflammation of the renal pelvis (kidney parenchyma results)
      • Presents with fever, urinary frequency, urgency, dysuria, and costovertebral angle tenderness
    •  Hydronephrosis:
      • Obstruction causes proximal accumulation of urine.
      • Results in the dilation of the renal pelvis and calyces (visible on ultrasound)

Clinical Presentation and Diagnosis

Clinical presentation

  • Depends on the size, number, and location of the stones
  • Small stones may be asymptomatic.
  • Stones within the renal pelvis and bladder are usually asymptomatic.
  • Symptoms are usually associated with acute ureteral obstruction:
    • Unilateral, colicky abdominal pain due to intermittent ureteral peristalsis: 
      • Colicky pain radiates to the groin, testes, or labia majora
      • Causes costovertebral angle tenderness
      • Usually associated with inability to lie still
    • Hematuria due to trauma to the ureter (frank or microscopic)
    • Nausea and/or vomiting
    • Fever suggests associated infection or pyelonephritis.

Diagnosis

Imaging:

  • Noncontrast CT of the abdomen and pelvis:
    • Gold-standard of imaging for kidney stones
    • Can show location and size of the stone
    • Can detect hydronephrosis
  • Abdominal ultrasound: used in pregnant women and children to avoid radiation
  • Abdominal X-ray: can detect large stones

Laboratory studies:

  • Urinalysis and urine dipstick:
    • Useful for detecting microscopic hematuria
    • Determines urine pH and helps determine the type of stone
  • Urine microscopy: evaluates the shape of the crystals
Renal calculus on ultrasound and CT

Left: White arrow shows renal calculus on ultrasound.
Right: White arrow shows renal calculus on CT scan.

Image: “US detection of renal and ureteral calculi in patients with suspected renal colic” by Vallone, G. et al. License: CC BY 2.0

Management

Size-based approach

  • < 5 mm: observation only (spontaneous passage is likely)
  • 5–10 mm: alpha-blockers or dihydropyridine calcium channel blockers
  • 10–20 mm: extracorporeal shock wave lithotripsy (ESWL) or ureterorenoscopy
  • > 20 mm: percutaneous nephrolithotomy

Medical management

General supportive care:

  • Hydration with IV fluid
  • Analgesic medications (pain can be severe)
  • Alpha-blockers (e.g., terazosin, tamsulosin) or dihydropyridine calcium channel blockers (e.g., nifedipine) to dilate and relax the ureters and allow for passage of stones < 10 mm

Stone-specific management:

  • Calcium oxalate and calcium phosphate stones:
    • Low-sodium diet to increase concomitant sodium and calcium reabsorption in proximal tubules
    • Citrate to dissolve calcium oxalate crystals
    • Thiazide diuretics to increase calcium reabsorption in the distal tubule
  • Struvite stones: antibiotic therapy to eliminate the causative microbe
  • Uric acid stones:
    • Urine alkalinization with potassium citrate to dissolve uric acid crystals
    • Allopurinol to decrease uric acid production
  • Cystine stones: tiopronin or penicillamine to chelate cystine

Surgical management

  • ESWL:
    • Stone fragmentation with sound waves
    • Not routinely performed in obese patients due to poor penetration of sound waves
  • Ureterorenoscopy: a transurethral endoscopic procedure to visualize the entire urinary tract and retrieve the kidney stone
  • Percutaneous nephrolithotomy: a surgical procedure with skin incision to retrieve the kidney stone

Prevention

  • Adequate hydration
  • Low-sodium, low-protein diet

Differential Diagnosis

  • Acute appendicitis: inflammation of the appendix caused by impaction of a fecalith in adults, or by lymphoid hyperplasia in children. The initial presentation is diffuse periumbilical pain, which then localizes to the RLQ. In contrast, nephrolithiasis causes flank pain. The diagnosis of appendicitis is mostly clinical and treatment is an appendectomy. 
  • Testicular torsion: the twisting of the spermatic cord caused by increased testicular mobility in the scrotal sac. Presentation includes erythema, swelling, absent cremasteric reflex, and sudden-onset, severe testicular pain. In contrast, nephrolithiasis-induced pain originates in the flank and later radiates to the groin. Diagnosis of testicular torsion is via Doppler ultrasound. Treatment is manual, or surgical detorsion with bilateral orchiopexy. 
  • Biliary colic: a colicky, RUQ pain caused by intermittent obstruction of the cystic duct by the gallstone. Presentation is episodic pain, especially after ingestion of a fatty meal. In contrast, pain due to nephrolithiasis is not related to eating. Diagnosis is based on the combination of clinical signs and RUQ ultrasound findings. Unless the patient develops acute cholecystitis, treatment is observation.
  • Diverticulitis: an inflammation of diverticula caused by the impaction of a fecalith. Presentation may include LLQ pain, moderate to high fever, and bloody stools. In contrast, nephrolithiasis is not characterized by bloody stools. Diverticulitis is diagnosed with a CT scan of the abdomen and most cases are treated with IV antibiotics. 

References

  1. Dave, N. C. (2020). Nephrolithiasis differential diagnoses. Medscape. Retrieved March 6, 2021, from https://emedicine.medscape.com/article/437096-differential
  2. Curhan, G. C. (2020). Kidney stones in adults: Epidemiology and risk factors. UpToDate. Retrieved March 6, 2021, from https://www.uptodate.com/contents/kidney-stones-in-adults-epidemiology-and-risk-factors
  3. Curhan, G. C. (2021). Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis. UpToDate. Retrieved March 6, 2021, from https://www.uptodate.com/contents/diagnosis-and-acute-management-of-suspected-nephrolithiasis-in-adults

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