What is the next step in the workup for a 75-year-old patient with impaired renal function (increasing creatinine) and suspected acute interstitial nephritis?

Workup for Suspected Acute Interstitial Nephritis in a 75-Year-Old with Rising Creatinine

The immediate next steps are: obtain urinalysis with microscopy looking specifically for eosinophils and white blood cell casts, perform a comprehensive medication review identifying all nephrotoxic agents (especially antibiotics, NSAIDs, PPIs, and diuretics), assess volume status and recent contrast exposure, and consult nephrology for consideration of kidney biopsy if no alternative cause is identified. 1

Initial Diagnostic Evaluation

Urinalysis and Urine Microscopy

• Obtain urinalysis immediately to look for sterile pyuria (≥5 WBCs/hpf), which supports probable drug-induced AIN when combined with sustained creatinine elevation ≥50%. 1
• Search specifically for eosinophiluria, as the presence of urinary eosinophils strongly suggests AIN, though their absence does not exclude the diagnosis. 2, 3
• Look for white blood cell casts and tubular epithelial cells, which indicate tubulointerstitial inflammation. 2
• Expect nonnephrotic range proteinuria (typically <3.5 g/day) rather than heavy proteinuria. 2

Comprehensive Medication Review

• Systematically review ALL medications—prescribed, over-the-counter, herbals, and vitamins—as the causative agent must be identified and discontinued. 1
• Focus particularly on:
  • Antibiotics (especially penicillins, cephalosporins, fluoroquinolones) 2, 3, 4
  • NSAIDs (including COX-2 inhibitors) 2, 5, 3, 4
  • Proton pump inhibitors (omeprazole, pantoprazole, etc.) 2, 6
  • Diuretics (thiazides, loop diuretics) 3, 4
  • Allopurinol, sulfonamides, cimetidine 4
• Document the timing of medication initiation relative to creatinine rise—AIN typically develops 2-18 months after drug exposure, though it can occur within weeks. 5, 6

Exclude Alternative Causes of AKI

• Assess for recent IV contrast exposure within the past 48-72 hours. 1
• Evaluate volume status clinically (orthostatic vital signs, mucous membranes, skin turgor, jugular venous pressure) to exclude prerenal azotemia. 1
• Rule out urinary tract infection with urine culture. 1
• Check for urinary obstruction with renal ultrasound if clinically indicated (though obstruction accounts for <3% of AKI cases). 1

Laboratory Assessment

• Monitor serum creatinine at least weekly to track progression or improvement. 1
• Check for peripheral eosinophilia (≥500 cells/mL), which supports the diagnosis when present alongside other findings. 1
• Obtain complete blood count, electrolytes, and assess for hyperkalemia or metabolic acidosis. 1

Clinical Presentation Clues

Classic Triad (Rarely Present)

• The classic triad of fever, rash, and eosinophilia is present in less than 10-15% of cases, so its absence does not exclude AIN. 2, 3
• Most patients present with nonspecific symptoms: malaise, nausea, vomiting, and nonoliguric AKI. 2
• Some patients may report flank pain, arthralgias, or fatigue. 6

Nephrology Consultation and Kidney Biopsy

When to Consult Nephrology

• Consult nephrology immediately for any patient with creatinine 2-3× baseline (Grade 2) or higher. 1
• Nephrology consultation is appropriate even at lower grades if AIN is suspected and alternative causes have been excluded. 1

Kidney Biopsy Indications

• If no potential alternative cause of AKI is identified after thorough evaluation, proceed directly with empiric treatment and forego biopsy initially. 1
• Reflex kidney biopsy should be discouraged until steroid treatment has been attempted for 5-7 days without improvement. 1
• Biopsy is indicated when:
  • Diagnosis remains uncertain after excluding other causes 2
  • No improvement occurs after 5-7 days of withdrawing the suspected drug 2, 3
  • Renal function continues to worsen despite drug withdrawal 2

Expected Biopsy Findings

• Extensive interstitial infiltrate predominantly composed of lymphocytes and monocytes, with variable numbers of eosinophils, plasma cells, and histiocytes. 2, 3
• Normal glomeruli (distinguishing AIN from glomerulonephritis). 3
• Patchy but usually heavy interstitial inflammation. 3

Management Algorithm

Immediate Actions

1. Discontinue the suspected causative drug immediately—this is the cornerstone of treatment. 2, 3, 4
2. Stop all nephrotoxic medications if possible (NSAIDs, ACE inhibitors/ARBs in volume depletion, aminoglycosides). 1
3. Ensure adequate hydration and avoid further nephrotoxic exposures. 1

Corticosteroid Therapy

• If there is no evidence of kidney function recovery after 5-7 days since discontinuing the suspected drug, initiate prednisone 1 mg/kg/day (or 0.5-1 mg/kg/day for Grade 2). 1, 2
• Early corticosteroid therapy (within 7 days of diagnosis) may decrease interstitial inflammation and prevent progression to irreversible fibrosis. 2, 3
• For Grade 3 or higher (creatinine ≥3× baseline or ≥4.0 mg/dL), start with 1-2 mg/kg/day prednisone equivalents. 1

Common Pitfalls to Avoid

• Do not wait for the classic triad (fever, rash, eosinophilia) to suspect AIN—it is rarely present. 2, 3
• Do not perform reflex kidney biopsy before attempting drug withdrawal and empiric steroid therapy if no alternative cause is found. 1
• Do not overlook proton pump inhibitors as a cause—they are increasingly recognized as culprits for AIN. 2, 6
• Do not continue the offending medication while "monitoring"—immediate discontinuation is essential to prevent irreversible fibrosis. 2, 3, 4
• Do not assume normal renal function will return without intervention—delayed treatment increases risk of chronic kidney disease. 2, 3

Prognosis and Follow-up

• Most cases of drug-induced AIN are fully reversible with prompt drug discontinuation, especially when detected early. 5, 3, 4
• Recovery typically occurs within 2 weeks to several months after stopping the causative agent. 6, 3
• Evaluate patients 3 months after AKI for resolution, new onset, or worsening of pre-existing CKD. 1
• Patients who recover should avoid re-exposure to the causative drug class, as rechallenge can precipitate recurrent AIN. 2