Renal · Year 2 · from Renal
Case 3: Acute Interstitial Nephritis from Proton Pump Inhibitor
Patient Presentation
A 54-year-old female presents with fatigue and mild flank discomfort. Laboratory studies ordered for pre-operative evaluation (elective knee replacement) revealed unexpected renal dysfunction.
History of Present Illness
- Routine pre-operative labs showed elevated creatinine
- Mild bilateral flank discomfort for 2 weeks
- No dysuria or gross hematuria
- Started omeprazole 20 mg daily 3 months ago for GERD
- No recent antibiotic use
- No fever or rash reported
Physical Examination
- Blood pressure: 138/84 mmHg
- Heart rate: 76 bpm
- Temperature: 37.0°C
- No rash
- Mild bilateral costovertebral angle tenderness
- No peripheral edema
Workup
Laboratory Studies:
- Creatinine 1 year ago: 0.9 mg/dL
- Current creatinine: 2.4 mg/dL
- BUN: 34 mg/dL
- WBC: 8,200/mcL with 6% eosinophils (480/mcL)
- Urinalysis: 2+ protein, 25 WBC/hpf, no bacteria, occasional WBC casts
- Urine eosinophils: Present (though low sensitivity)
- Urine culture: Negative
Renal Biopsy:
- Interstitial edema with lymphocytic infiltrate and scattered eosinophils
- Tubulitis present
- No granulomas
- Glomeruli normal
Diagnosis
Proton Pump Inhibitor-Induced Acute Interstitial Nephritis
Discussion
This case illustrates drug-induced AIN:
- PPI-Associated AIN: The lecture notes that PPIs have emerged as an increasingly recognized cause of AIN, often with insidious onset weeks to months after starting therapy (unlike the 1-3 week onset typical of beta-lactams).
- Classic Triad Absent: The lecture emphasizes that the complete triad of fever, rash, and eosinophilia occurs in <10% of cases. This patient had only mild eosinophilia.
- Sterile Pyuria with WBC Casts: These findings support interstitial inflammation rather than infection. WBC casts are characteristic of AIN, as noted in the lecture.
- Idiosyncratic Reaction: AIN is not dose-dependent; it represents a type IV hypersensitivity reaction where the drug acts as a hapten.
- Biopsy Findings: Interstitial edema, lymphocytic infiltrate, tubulitis, and eosinophils confirm the diagnosis.
Treatment
- Discontinue omeprazole
- Switch to H2 blocker (famotidine) for GERD
- Observe for improvement over 1 week
- If no improvement, start prednisone 1 mg/kg/day for 2-4 weeks with taper
- Elective surgery postponed until renal function improves
- Creatinine improved to 1.3 mg/dL at 3 weeks
Clinical Pearl
PPI-induced AIN has a longer latency period (weeks to months) compared to classic antibiotic-induced AIN. The absence of fever and rash is common, making clinical suspicion essential. Withdrawal of the offending agent is the cornerstone of treatment; steroids may accelerate recovery if improvement does not occur within 1 week.
Image Reference
For visual reference of AKI concepts, see:
- Radiopaedia: Acute tubular necrosis - Histology and clinical information
- Wikimedia Commons: Kidney histology - Normal and pathologic tubular structures
- Radiopaedia: Acute interstitial nephritis - Biopsy findings
Learning Points
- FENa Distinguishes Prerenal from ATN: FENa <1% with concentrated urine suggests prerenal AKI with intact tubular function; FENa >2% with isosthenuria suggests ATN.
- Urinary Sediment is Diagnostic: Bland sediment (hyaline casts only) supports prerenal; muddy brown casts indicate ATN; WBC casts suggest AIN or pyelonephritis.
- Drug-Induced AIN Classic Triad is Rare: Fever, rash, and eosinophilia together occur in <10% of cases. Maintain suspicion based on timing and clinical context.
- PPIs Have Delayed Onset AIN: Unlike beta-lactams (1-3 weeks), PPI-induced AIN may develop months after starting therapy.
- AEIOU for Dialysis Indications: Acidosis (refractory), Electrolytes (hyperkalemia), Intoxication (dialyzable toxins), Overload (volume), Uremia (symptomatic) - memorize these indications for emergency dialysis.