03. Acute Interstitial Nephritis

Background

  • AIN is inflammation and scarring in the tubular and interstitial compartments, sparing the glomeruli.
  • Accounts for 10% of in-hospital AKI.
  • Often an immune-mediated allergic reaction to a medication.
  • A drug rash, new medication, sterile pyuria, and eosinophilia are suggestive, but not definitive.

Etiology

  • Immune-mediated:
  • Drug hypersensitivity: PCN and derivatives, NSAIDs, PPIs, cephalosporins, sulfa-containing drugs (e.g., HCTZ, furosemide), quinolones, anticonvulsants (phenytoin, carbamazepine, phenobarbital), allopurinol, rifampin, mesalamine, plus many rare causes.
  • PCN-associated:
  • 90% of cases involve hematuria.
  • Serum eosinophilia is a common feature.
  • Low level proteinuria may be present.
  • NSAID-associated:
  • Serum eosinophilia is present in 40% of cases but complete triad of fever, rash, and eosinophilia is uncommon.
  • 90% of NSAID-associated AIN leads to AKI, with progression to HD in one-third of cases.
  • 70% of cases are associated with the nephrotic syndrome due to concomitant minimal change disease.
  • Systemic disease: transplant rejection, sarcoidosis, Sjögren’s syndrome, SLE, lymphoma, leukemia, IgG4.
  • Associated with glomerulonephritis: lupus nephritis, IgA nephropathy.
  • Infection-mediated:
  • Bacterial pyelonephritis.
  • Systemic infection:
  • Bacterial: beta-hemolytic streptococcus, legionella, brucella, mycoplasma, leptospirosis.
  • Viral: EBV, HIV, Hantavirus, CMV.
  • Fungal: histoplasmosis.
  • Idiopathic:
  • Includes the TINU syndrome (tubulointerstitial nephritis and uveitis).
  • Uveitis may occur weeks before to 3 months after the AIN.
  • Other signs include elevated ESR, weight loss and anemia.

Evaluation

  • The classic triad of rash, fever and arthralgias (indicative of systemic hypersensitivity) is present in the minority of cases.
  • Work-up: CBC with differential (eosinophilia when present is helpful although it is neither sensitive nor specific), chem10, UA with microscopy, urinary sediment examination (WBC casts, eosinophils, crystals, +/- RBCs).
  • Kidney biopsy is the only definitive diagnostic test.

Management

  • Treatment: the most important factor is identification and discontinuation of offending medications (or treatment of underlying infection).
  • Steroids (prednisone 1 mg/kg up to 60 kg daily) may improve outcomes, especially if used early.
  • Prognosis: outcome is typically favorable with 64% of patients recovering full kidney function and another 23% with partial recovery. Only 10% progressed to RRT.

Key Points

  • AIN is often an allergic reaction to medication or due to infection.
  • Identification and discontinuation of the offending medication (or treatment of the underlying infection) is the most important treatment.
  • WBC with a negative leukocyte esterase may be a clue to eosinophiluria (although this is neither sensitive nor specific).

 

González E, Gutiérrez E, Galeano C, et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int. 2008;73(8):940-6

Perazella MA. Toxic nephropathies: core curriculum 2010. Am J Kidney Dis. 2010;55(2):399-409.

Praga M, González E. Acute interstitial nephritis. Kidney Int. 2010;77(11):956-61

Praga M, Sevillano A, Auñón P, González E. Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury. Nephrol Dial Transplant. 2014.