Shane M. Meehan, MBBCh

Polarized light reveals spiderweb-like organic stone matrix with calcium oxalate in radial arrays image located in the suburothelium of the renal pelvis.

Renal calyx, viewed using partially polarized light, contains refractile crystalline material embedded in organic matrix with an irregular laminated structure.



  • Kidney stone disease, renal stone disease, renal calculi, urolithiasis, lithiasis


  • Concretion of urinary mineral or inorganic crystals in collecting system of kidney


Stone Types by Mineral Content

  • Calcium-containing stones (~ 80% of all stones) are composed of the following compounds

    • Calcium oxalate (30%)

    • Calcium oxalate and calcium phosphate (35-45%)

    • Calcium phosphate: Hydroxyapatite (3.75-6%)

    • Calcium monohydrogen phosphate: Brushite (1.25-2%)

  • Struvite (magnesium-ammonium phosphate and calcium carbonate-apatite) (5-10%)

  • Uric acid (5-10%)

  • Cystine (1-2%)

  • Miscellaneous: Xanthine, 2,8-dihydroxyadenine, drugs (e.g., indinavir, sulphadiazine, silica-containing antacids), melamine

Predisposing Factors

  • Calcium stones

    • Hypercalciuria (defined as > 4 mg Ca/kg/day in urine) without hypercalcemia

      • Idiopathic

      • Renal tubular acidosis

      • Medullary sponge kidney

      • Cadmium and beryllium nephrotoxicity

    • Hypercalcemia and hypercalciuria: Primary and secondary hyperparathyroidism

    • Hyperoxaluria

      • Primary: Autosomal recessive, types I and II

      • Secondary: Enteric, due to small intestinal malabsorption or excess intake; dietary, due to poisoning (ethylene glycol)

  • Struvite stones

    • Infection by urea-splitting organisms: Proteus, Pseudomonas, Providencia species and others

    • Alkaline urine increases risk

  • Uric acid stones

    • Hyperuricosuria

      • Associated with uric acid lithiasis and with ~ 40% of calcium oxalate lithiasis

    • Acidic urine with pH < 5.5

  • Cystine stones

    • Hereditary disorders of tubular transport with mutations of solute-linked carriers 3A1 and 7A9 genes

  • General

    • Low urine volume

Pathophysiology of Stone Formation

  • Urine is supersaturated with stone constituents

  • Nucleation is condensation of dissolved salts to solid phase crystals

    • Homogeneous nucleation: When solubility limits are exceeded

    • Heterogeneous nucleation: Cell membranes, cell debris, or other types of crystal form a nidus

    • Heterogeneous nucleation occurs at lower supersaturation than homogeneous nucleation

  • Randall plaque

    • Deposition of calcium phosphate as hydroxyapatite (apatite) in renal papillae

    • Apatite deposits grow beneath papillary urothelium and around Bellini ducts forming Randall plaque

    • Randall plaque is thought to be heterogeneous nucleation site for calcium oxalate stone formation

  • Brushite, hydroxyapatite, and cystine stones can develop from deposits within Bellini ducts

  • Stone composition: About 95% aggregated crystals and 5% organic mucoprotein matrix

    • Cut surface of stone has concentrically laminated appearance

    • Concentric layers are organic matrix skeleton, and crystalline aggregates are in radial arrays

Causes of Nephrolithiasis

  • 25% known causes

    • Primary hyperparathyroidism and other causes of hypercalcemia

    • Renal tubular acidosis

    • Hyperoxaluria

    • Medullary sponge kidney

    • Drugs: Antivirals (acyclovir, ganciclovir, indinavir), sulfonamide derivatives, triamterene, glafenine, pyridoxylate

  • 50% idiopathic hypercalciuria

  • 25% unknown cause



  • Frequency: 5% of females and 12% of males in USA

  • Nonobstructive stones have only hematuria without other symptoms or signs

  • Renal colic is associated with stone passage, which is dependent on stone size

    • < 5 mm: High chance of passage

    • 5-7 mm: ~ 50% chance of passage

    • > 7 mm: Requires intervention for removal


  • Extracorporeal shock wave lithotripsy utilizes ultrasonic waves to break up stones

  • Endoscopic laser-guided stone disruption

  • Percutaneous nephrostomy permits removal of larger stones

  • Medical treatment includes hydration to increase urinary volume and thiazide diuretics to reduce calcium excretion


  • Stones recur in ~ 50% of instances

  • Stone formers have higher blood pressure than nonstone formers

  • Stone formers with high body mass index (> 27) have lower GFR than matched nonstone formers

  • Almost any stone type can be complicated by urinary obstruction or infection


Morphology of Common Stone Types

  • Calcium oxalate and apatite

    • Solitary or multiple; hard, radiopaque; yellow-brown

  • Struvite

    • Large and branched (“staghorn”); hard, gray-white, radiopacity dependent on calcium content

  • Uric acid

    • Multiple; seldom > 2 cm; hard, smooth surface, yellow-brown; mainly radiolucent

  • Cystine

    • Multiple; small, smooth, rounded (rarely “staghorn”); yellow, waxy, radiopaque

  • 80% of stones are unilateral

  • Stones protrude from Bellini ducts in calcium phosphate, uric acid, cystine, and some cases of enteric oxaluria associated lithiasis


Histologic Features

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Nephrolithiasis

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