Description

• Nephrocalcinosis (NC) is a condition in which there is deposition of calcium in the renal parenchyma and tubules.
• NC refers to the deposition of both calcium phosphate and calcium oxalate crystals, but the most important criterion is the generalized deposition of calcium in the kidney.
• They are classified based on
  • Molecular/chemical—measurable increase in the intracellular calcium concentration but is not visible microscopically or via imaging techniques
  • Microscopic—calcium mineral deposits visible microscopically but not by imaging techniques
  • Macroscopic—calcium is visible by radiographic imaging (1)
• NC primarily involves the renal medulla. Cortical NC occur usually due to underlying cortical disease such as those associated with pregnancy, chronic glomerulonephritis, or renal allograft rejection.
• The degree of kidney injury can vary: may present with acute or chronic renal failure or continue to have normal renal function
• NC is a slow progressive, chronic, often asymptomatic disease, usually diagnosed incidentally.

Epidemiology

Incidence
Difficult to determine due to multiple etiologies

Prevalence

• 7–41% of preterm newborns (2)
• Up to 20% of patients with hyperparathyroidism
• UTI was associated with development of NC in neonates that resolved on its own without surgical intervention.

Etiology and Pathophysiology

• NC is predisposed by increased urinary calcium, oxalate, and phosphate excretion. The crystals can be either homogenous or heterogeneous. This increased concentration of reactants often exceeds the saturation limit, and deposits occur primarily in the inner medullary interstitium in the basement membrane of thin limbs of loop of Henle.
• High alkaline pH is seen in patients with calcium phosphate NC.

Genetics
Increased prevalence of NC with certain hereditary disorders:

• Dent disease
• Lowe syndrome (oculocerebrorenal syndrome)
• Familial hypomagnesemia with hypercalciuria and NC
• Primary hyperoxaluria
• Bartter syndrome
• Liddle syndrome (3)
• Williams-Beuren syndrome
• Congenital adrenal hyperplasia

Risk Factors

• Medullary
  • Primary hyperparathyroidism
  • Renal tubular acidosis (RTA)
  • Prematurity
  • Hereditary disorders
  • Hyperthyroidism
  • Granulomatous diseases such as sarcoidosis
  • Oversupplementation of phosphate and vitamin D
  • Multiple myeloma
  • Cushing syndrome
  • Chronic steroid use
  • Metastatic neoplasm
  • Medullary sponge kidney
  • Milk-alkali syndrome
  • Hyperuricemia
  • Sickle cell disease
  • Drug induced: pamidronate and loop diuretics
  • Sjögren disease
  • Chronic hypokalemia
  • Tumor lysis syndrome, acute phosphate nephropathy, enteric hyperoxaluria < acute presentation
• Cortical
  • Renal infarct, ischemia, or toxins
  • Hyperoxaluria
  • Chronic glomerulonephritis
  • Alport syndrome
  • Autosomal recessive polycystic kidney disease
  • Opportunistic intrarenal infections such as Mycobacterium avium or Pneumocystis carinii pneumonia
• Other method of classification
  • Hypercalciuria with hypercalcemia
    • Primary hyperparathyroidism
    • Overdose of vitamin D and phosphate
    • Sarcoidosis
    • Milk-alkali syndrome
    • Williams syndrome
    • Congenital hypothyroidism
  • Hypercalciuria without hypocalcemia
    • Distal RTA
    • Neonatal NC
    • Loop diuretics
    • β-Thalassemia
    • Chronic hypokalemia
    • Medullary sponge kidney
    • Inherited tubulopathies
      • Bartter syndrome
      • Gitelman syndrome
      • Hypomagnesemic hypercalciuric NC
  • Hyperphosphaturia
    • Hyperoxaluria

General Prevention

• Prevention of preterm birth
• Genetic counseling

Commonly Associated Conditions

• Hypercalcemia
• Hypercalciuria
• Hyperphosphaturia
• RTA
• Hyperoxaluria
• Urinary stasis
• Hyperparathyroidism
• Treatment of hypoparathyroidism
• Medullary sponge kidney
• Osteoporosis