Kidney stone pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Pathophysiology

Pathogenesis

• It is understood that nephrolithiasis is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
• [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
• Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
• [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
• The progression to [disease name] usually involves the [molecular pathway].
• The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

• Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria:
  • Hereditary distal renal tubular acidosis
  • Dent disease
  • Bartter syndrome types III and IV
  • Autosomal dominant hypocalcemic hypercalciuria
  • Familial hypomagnesemia

Associated Conditions

• Hyperparathyroidism
• Gout
• Hypocitaturia
• Sarcoidosis
• Chronic urinary tract infections
• Obesity

Gross Pathology

• On gross pathology,the characteristic findings of nephrolithiasis are:
  • Location = 80% unilateral, usually in calyces, pelvis or bladder
  • Size=variable, 2-3 mm usually
  • All stones contain an organic matrix of mucoprotein
  • Shape=
    • Struvite stone= staghorn calculus

• 

  Nephrolithiasis, Source: Wikimedia commons

• 

  Staghorn shape of struvite stones, Source: Wikimedia commons

• 

  Renal calculi, different shapes and sizes, Source: Wikimedia commons

• 

  Kidney stone with a maximum dimension of 5mm, Source: Wikimedia commons

Microscopic Pathology

• On microscopic histopathological analysis, the characteristic findings of nephrolithiasis are:
  • Shapes of different stones/crystals are different
    • Cysteine=hexagonal
    • Struvite= coffin lid shape
    • Calcium oxalate=pyramid shape
    • Calcium oxalate= dumbbell shaped
    • Uric acid= rectangular/rhomboidal
  • Oxalate crystals are highlighted by polarized light
  • Foreign body giant cells and macrophages are seen with the stones

• 

  Type of stones. Light microscopy of urine crystals. (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X).

• 

  Deposits of oxalate with variable size and form; they occupy mainly distal tubules. The asterisks indicate proximal tubules, which usually do not contain these crystals, H&E seen with polarized light, X200

• 

  Medullary interstitial urate crystal deposits in chronic nephropathy by urates as seen after Masson's trichome stain X400

• 

  Calcium oxalate dihydrate crystals under Scanning Electron Micrograph (SEM) taken at 30 KV. Source: Wikimedia commons

• 

  Density-dependent color scanning electron micrograph of kidney stone, Source: Wikimedia commons