Renal · Year 2 · from Renal

Case 1: Drug-Induced Acute Interstitial Nephritis

Patient Presentation

Demographics: 45-year-old female

Chief Complaint: Elevated creatinine found on routine labs

History of Present Illness: The patient was started on omeprazole 20 mg daily 2 months ago for gastroesophageal reflux disease. She presents for routine follow-up and is found to have elevated creatinine. She reports mild fatigue and occasional bilateral flank discomfort but denies fever, rash, dysuria, or gross hematuria. She had no prior kidney disease.

Past Medical History:

  • GERD (recently diagnosed)
  • Hypertension
  • No prior kidney disease

Medications:

  • Omeprazole 20 mg daily (started 2 months ago)
  • Lisinopril 10 mg daily (stable for years)

Physical Examination:

  • Blood pressure: 132/82 mmHg
  • Temperature: 37.0C
  • General: Well-appearing
  • Skin: No rash
  • Lungs: Clear
  • Abdomen: Mild bilateral CVA tenderness
  • Extremities: No edema

Workup and Results

Laboratory Studies:

  • Creatinine: 2.1 mg/dL (baseline 0.9 mg/dL 4 months ago)
  • BUN: 28 mg/dL
  • Potassium: 4.8 mEq/L
  • WBC: 9,200/mcL with 8% eosinophils (736/mcL)
  • Urinalysis: 1+ protein, no blood, 30 WBC/hpf, occasional WBC casts
  • Urine culture: Negative
  • Urine eosinophils: Present

Renal Biopsy:

  • Interstitial edema with lymphocytic infiltrate
  • Eosinophils present in interstitium
  • Tubulitis
  • Glomeruli: Normal
  • No granulomas

Clinical Image

Renal biopsy showing acute interstitial nephritis with interstitial edema, lymphocytic infiltration, scattered eosinophils, and tubulitis (lymphocytes invading tubular epithelium).

Diagnosis

Proton Pump Inhibitor-Induced Acute Interstitial Nephritis

Features supporting diagnosis:

  • Temporal relationship with PPI initiation
  • Sterile pyuria with WBC casts
  • Mild peripheral eosinophilia
  • Biopsy confirmation

Discussion

This case illustrates drug-induced AIN:

  • PPI-Associated AIN: The lecture notes that PPIs have emerged as an increasingly recognized cause of AIN. Unlike beta-lactam antibiotics (1-3 week onset), PPI-induced AIN often has insidious onset weeks to months after starting therapy.
  • Classic Triad Absent: The lecture emphasizes that the complete triad of fever, rash, and eosinophilia occurs in <10% of AIN cases. This patient had only mild eosinophilia without fever or rash.
  • Type IV Hypersensitivity: Drug-induced AIN represents a delayed-type hypersensitivity reaction where the drug acts as a hapten, not a dose-dependent toxicity.
  • WBC Casts: The lecture identifies WBC casts as characteristic of AIN or pyelonephritis, distinguishing interstitial from glomerular disease.
  • Urine Eosinophils: The lecture notes urine eosinophils have low sensitivity (40-60%) but can support the diagnosis when present.

Treatment Plan

  1. Discontinue Omeprazole:
  • Switch to H2 blocker (famotidine) for GERD
  • Avoid all PPIs in the future
  1. Observation Period:
  • Monitor creatinine for 1 week after drug discontinuation
  • Many patients improve with drug withdrawal alone
  1. Corticosteroids (if no improvement):
  • Prednisone 1 mg/kg/day for 2-4 weeks
  • Taper over 4-6 weeks
  • Consider if no improvement within 1 week
  1. Follow-up:
  • Creatinine improved to 1.2 mg/dL at 4 weeks
  • Document PPI allergy in medical record

Teaching Points

  1. PPIs cause AIN with delayed onset (weeks to months)
  2. Classic triad of fever, rash, eosinophilia is present in <10% of cases
  3. WBC casts and sterile pyuria suggest interstitial nephritis
  4. Withdrawal of offending agent is the cornerstone of treatment

All cases for this lecture as Markdown