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Nephrocalcinosis

❓What❓

  • “Nephrocalcinosis” refers to the deposition of calcium salts (calcium oxalate, calcium phosphate) in the kidney parenchyma & tubules, which can result from a variety of conditions that lead to ↑ urinary calcium, phosphate, and/or oxalate

  • Regardless of whether disease is “microscopic” (image ⊖) or “macroscopic” (image ⊕), renal dysfunction as a result of tubulointerstitial inflammation ensues (AKI-CKD)

  • Specifically, calcium phosphate crystallization primarily occurs within the inner medullary interstitium, with resultant tubular rupture serving as a nidus for intraluminal crystallization; meanwhile, calcium oxalate crystallization has been described to occur primarily intraluminally, with subsequent plugging resulting in diffuse nephron obstruction & renal dysfunction

❓Epidemiology❓

  • ↑ urinary calcium, phosphate, & oxalate are closely associated with nephrolithiasis, thus nephrocalcinosis patients frequently present with concurrent kidney stones. (However, these conditions also separately co-exist: this is readily apparent when you consider the vast majority of patients with kidney stones do not suffer nephrocalcinosis.)

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❓Presentation❓

Radiographic 🩻

  • Image ⊕: calcium deposits within the kidney medulla > cortex
  • Image ⊖: “microscopic” nephrocalcinosis (can still cause AKI)

Laboratory 🔬

  • Intra-renal AKI-CKD
  • UA normal, sterile pyuria (inflammation), hematuria (intraluminal bleeding)
  • ↑ 24-hour urine calcium, phosphate, oxalate

Microscopic view of calcium oxalate crystals in the urine
Microscopic view of calcium oxalate crystals in the urine

Clinical, Renal 😖

  • Nephrolithiasis ⊕: renal colic, gross hematuria
  • Nephrolithiasis ⊖: risk factor clue (e.g. diarrhea of malabsorption of oxalosis)

Risk Factor (Acquired) 🧠

Hypercalcemia → ↑ Urine Calcium

  • Hypercalcemia DDx, emphasis on …
    • Primary hyperparathyroidism
    • Vitamin D excess, Milk alkali syndrome
    • Granulomatous disorders (e.g. chronic sarcoidosis)

↑ Urine Calcium ⊕ Normal Serum Calcium

  • Type 1 RTA DDx
  • Chronic loop diuretic ⊕ Bartter syndrome
  • Dent disease

Hyperphosphatemia → ↑ Urine Phosphate

  • Tumor lysis syndrome (acute vs. chronic)
  • Discontinued phosphate-based bowel preps

Fat Malabsorption → ↑ Oxalate Absorption → ↑ Urine Oxalate

  • Exocrine pancreatic insufficiency
  • Gastric bypass surgeries vs. bowel resection
  • Inflammatory bowel disease, Celiac disease
  • GLP1R agonists

Clinical, Extrarenal = Oxalosis (Infiltrative) ⚪

  • Skin: subcutaneous nodules
  • Marrow: cytopenias
  • Heart: blocks, ↓ voltage

❓Diagnosis❓

  • “Microscopic”: implies imaging is ⊖, thus diagnosis becomes reliant on combination of laboratory testing (serum calcium/phosphate, 24-hour urine calcium/phosphate/oxalate) vs kidney biopsy
  • “Macroscopic”: implies imaging is ⊕, with resultant endpoint DDx dependent on risk factors noted above
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📚 References 📚