What is the approach to managing acute interstitial nephritis?

Approach to Acute Interstitial Nephritis

Immediately discontinue all potential offending medications—particularly proton pump inhibitors, NSAIDs, and antibiotics—as this is the cornerstone of management and early drug withdrawal is the strongest predictor of renal recovery. 1, 2, 3

Initial Diagnostic Evaluation

Rule Out Alternative Causes of AKI

• Exclude hypovolemia, urinary obstruction, IV contrast exposure, and other nephrotoxic medications before confirming AIN 4, 1
• Assess fluid status, recent medication changes (including over-the-counter drugs, herbals, and vitamins), and recent procedures involving contrast 4
• Obtain urinalysis to rule out urinary tract infection and evaluate for sterile pyuria (≥5 WBCs/hpf), which supports AIN diagnosis 4, 2

Establish Severity Grading

• Grade 1: Creatinine increase >0.3 mg/dL or 1.5-2.0× baseline 4
• Grade 2: Creatinine 2-3× baseline 4
• Grade 3: Creatinine ≥3× baseline or ≥4.0 mg/dL; hospitalization indicated 4
• Grade 4: Life-threatening; dialysis indicated; creatinine ≥6× baseline 4

Consider Renal Biopsy

• Biopsy remains the gold standard for diagnosis but may not be necessary if temporal relationship is clear and improvement occurs after drug discontinuation 1, 2, 5
• Strongly consider biopsy when diagnosis is uncertain, steroid therapy is being contemplated, or no improvement occurs within 5-7 days of drug withdrawal 1, 5, 3
• Biopsy should be discouraged until steroid treatment has been attempted in immune checkpoint inhibitor-related cases 4

Management Algorithm by Severity

Grade 1 (Mild)

• Temporarily hold suspected offending agents 4
• Monitor creatinine closely; if improved to baseline, resume routine monitoring 4
• No corticosteroids needed if rapid improvement occurs 1

Grade 2 (Moderate)

• Immediately discontinue all suspected nephrotoxic drugs 4, 1
• Consult nephrology 4
• If no improvement after 5-7 days, initiate prednisone 0.5-1 mg/kg/day 4, 1
• If worsening or no improvement after 1 week on steroids, increase to 1-2 mg/kg/day prednisone 4
• Taper steroids over at least 4 weeks once improved to ≤Grade 1 4

Grade 3-4 (Severe)

• Hospitalize immediately 4, 1
• Permanently discontinue offending agent 4, 1
• Initiate IV methylprednisolone 1-2 mg/kg/day immediately 4, 1
• Monitor creatinine every 24 hours 1
• Transition to oral prednisone 1 mg/kg/day (maximum 80 mg/day) once stabilized 1
• Consider additional immunosuppression (infliximab, azathioprine, cyclophosphamide, cyclosporine, or mycophenolate) if no improvement after 2-5 days 4
• Taper steroids gradually over at least 4 weeks 4, 1

Special Considerations

Drug-Specific Risks

• NSAIDs carry the highest risk of permanent renal insufficiency (56% in NSAID-induced cases) 6
• Proton pump inhibitors are increasingly recognized as a major cause; monitor creatinine at 4-6 weeks after initiation and every 3-6 months for chronic users 2, 7
• Antibiotics are the most common class implicated overall, but typically have better outcomes than NSAID-induced AIN 7, 6

Prognostic Factors for Permanent Renal Damage

• Drug intake for >1 month prior to diagnosis predicts permanent insufficiency in 88% of cases 6
• Presence of tubular atrophy, interstitial granuloma, and pronounced interstitial infiltration on biopsy indicate chronicity 6
• Delayed drug withdrawal worsens prognosis; time to removal is the best predictor of recovery 6, 5

Monitoring During Treatment

• Check creatinine, electrolytes, and mental status daily during acute phase 1
• Monitor for steroid complications: provide calcium/vitamin D supplementation, monitor blood glucose, consider gastric protection 1
• Consider PJP prophylaxis if steroids continued >4 weeks 1
• Avoid nephrotoxin re-exposure during recovery phase to prevent re-injury 4

Critical Pitfalls to Avoid

• Do not delay drug discontinuation while awaiting biopsy results—early withdrawal is paramount 1, 3
• Do not miss relative creatinine changes: a 50% rise from baseline warrants investigation even if absolute value remains "normal" 1, 2
• Do not assume classic triad (fever, rash, eosinophilia) will be present—it occurs in <33% of cases 5, 3
• Do not continue nephrotoxins during the recovery phase of acute kidney disease, as this period represents critical vulnerability 4