Harvey's Garden

Tubulointerstitial diseases

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Acute tubulointerstitial nephritis

Definition

Acute tubulointerstitial nephritis (ATIN) is an acute inflammation of the renal interstitium and tubules that causes a decline in renal function over a period of days to weeks.

Etiology

Medications (most common)

Pathophysiology

  • Immune-mediated tubulointerstitial damage (allergic interstitial nephritis) is the most widely accepted theory.
    • Inflammatory infiltrates → tissue edema and tubular cell damage → compromised tubular flow
    • Allergic interstitial nephritis: drugs act as haptens → type IV hypersensitivity reaction
  • Acute obstruction: crystals (from e.g., uric acid, medications) or proteins (e.g., light chains) obstruct tubules

Clinical features

  • Onset is typically 7-10 days after starting the offending drug.
  • Classic Triad (present in only 10-15% of pts):
    • Fever
    • Rash (maculopapular)
    • Arthralgias
  • Features of Acute Kidney Injury (AKI): Oliguria, ↑ BUN, ↑ Cr.

Diagnostics

  • Labs:
    • Peripheral eosinophilia.
    • ↑ BUN and ↑ serum Cr.
  • Urinalysis (UA):
    • WBC casts (pathognomonic but not always present).
    • Sterile pyuria (WBCs in urine without bacteriuria).
    • Eosinophiluria (seen with Wright or Hansel stain; highly specific but not sensitive).
    • Mild proteinuria.
  • Renal Biopsy (definitive Dx, but not always required):
    • Interstitial inflammatory infiltrate (lymphocytes, macrophages, eosinophils).

Tip

Although frequently cited as a diagnostic clue, in clinical practice, urine eosinophils lack sensitivity and specificity for reliably confirming ATIN.

Treatment

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Crystalline nephropathies

Definition: a type of kidney injury that is triggered by crystal deposition and may lead to crystal-induced AKI, crystal-induced CKD, or urolithiasis

Epidemiology

Etiology

Drug-induced: e.g., acyclovir, indinavir, ciprofloxacin, methotrexate

Pathophysiology

Precipitation of minerals (crystallization) → phagocytosis of crystals → activation of the inflammasome → renal damage

Clinical features

Diagnostics

Crystals may be seen on urine microscopy.

Treatment

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Chronic tubulointerstitial nephritis

Chronic tubulointerstitial nephritis (CTIN) is a condition of chronic inflammation of the renal tubules and interstitium and can progress to end-stage renal disease (ESRD) after months or years.

Pathophysiology

  • Analgesic nephropathy (e.g., resulting from NSAIDs use)
    • Inhibition of prostacyclin synthesis → vasoconstriction of the medullary blood vessels → papillary ischemia and papillary necrosis
    • Associated with an increased risk of urothelial carcinoma; can progress to ESRD

Etiology

Clinical features

  • Painless hematuria, pyuria, oliguria, or polyuria
  • Colicky flank pain

Diagnostics

  • Blood tests: ↑ BUN and creatinine, ↓ K+ or ↑ K+; normal anion gap ; anemia of CKD
  • Urine chemistries in tubulointerstitial diseases (findings similar to ATIN): sterile pyuria, proteinuria, hematuria, RBC casts, WBC casts
  • Renal biopsy: tubulointerstitial fibrosis and tubular atrophy
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Renal papillary necrosis

Renal papillary necrosis is ischemic, coagulative necrosis of the renal medullary pyramids and papillae and is a feature of various conditions.

Epidemiology

Etiology

Pathophysiology

  • Coagulative necrosis of the renal papillae and medullary pyramids due to ischemia. The renal medulla is naturally a low oxygen tension environment, making it vulnerable to ischemic injury.
  • Ischemia can result from direct vascular obstruction (e.g., sickle cell), vasoconstriction (e.g., NSAIDs), or inflammation.

Clinical features

  • Can be asymptomatic and found incidentally.
  • Symptomatic patients may present with:
    • Acute flank pain and renal colic (due to obstruction by sloughed papillae).
      • Sloughed papillae can obstruct the ureters.
    • Gross or microscopic hematuria.
    • Fever and chills, especially if a superimposed infection (pyelonephritis) is present.
    • Passage of necrotic tissue in the urine.
  • Sudden deterioration of kidney function in a patient with a known risk factor (e.g., diabetes) should raise suspicion.

Acute tubular necrosis vs Renal papillary necrosis

Diagnostics

Treatment

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