What is the recommended treatment for acute interstitial nephritis with prednisone?

Treatment of Acute Interstitial Nephritis with Prednisone

For drug-induced acute interstitial nephritis, initiate oral prednisone at 1 mg/kg/day (or 60 mg/day) for 2-3 weeks, then taper over 2-3 weeks, with treatment most effective when started early after diagnosis. 1, 2

Initial Management

Immediately discontinue the offending drug - this is the most critical step in treating drug-induced AIN and must occur before or concurrent with steroid initiation. 1, 2 Common culprits include NSAIDs, proton pump inhibitors (especially pantoprazole), antibiotics (rifampicin, beta-lactams, fluoroquinolones), and other medications. 1, 2

Eliminate concurrent nephrotoxic exposures during treatment, as continued exposure to proton pump inhibitors or trimethoprim-sulfamethoxazole during steroid therapy significantly delays renal recovery (median 20 days vs 13 days). 3

Steroid Dosing Regimens

Standard Oral Regimen (Preferred for Most Cases)

• Start with oral prednisone 1 mg/kg/day (typically 60 mg/day maximum) for 2-3 weeks 1, 2
• Taper over 2-3 weeks to minimize adrenal suppression 1, 2
• Administer as a single morning dose before 9 AM to align with physiologic cortisol rhythm and minimize HPA axis suppression 4
• Give with food or milk to reduce gastric irritation 4

Pulse IV Methylprednisolone (Alternative, Not Superior)

• 30 mg/kg IV for 3 days (maximum 1 gram per dose) followed by oral prednisone 1 mg/kg/day for 2 weeks, then taper over 2-3 weeks 1, 2
• No significant advantage over oral therapy - both regimens achieve similar complete remission rates (56-61%) and partial remission rates (39-44%) 1, 2
• Consider for patients unable to take oral medications or with severe presentations 1

Rapid Taper Protocol (Emerging Evidence)

• Start prednisone 60 mg/day, taper to 10 mg within 3 weeks (versus traditional 6-week taper) 3
• Achieves similar renal recovery with reduced steroid exposure - 85% recovery by 30 days with rapid taper versus 46% with standard taper 3
• Median time to ≤10 mg/day: 20 days (rapid) vs 38 days (standard) 3

Special Population: Immune Checkpoint Inhibitor-Induced AIN

For ICI-related nephritis with Grade 2 creatinine elevation (2-3× baseline), start prednisone 0.5-1 mg/kg/day 5

For Grade 3-4 (creatinine ≥3× baseline or ≥4.0 mg/dL), initiate methylprednisolone 1-2 mg/kg/day IV 5

• Higher initial doses (methylprednisolone 500-1000 mg daily for 3 days) may be used in severe cases 6
• Permanently discontinue the checkpoint inhibitor if directly implicated in Grade 3-4 nephritis 5
• Taper steroids over at least 4 weeks once improved to Grade 1 5
• ICI rechallenge carries 13% risk of recurrent nephritis - weigh carefully against oncologic benefit 3

Monitoring Treatment Response

Assess response at 1 week - a ≥56% fall in serum creatinine predicts complete remission, versus 42% fall in partial responders 2

Define outcomes at 3 months:

• Complete remission: eGFR ≥60 mL/min/1.73 m² 1, 2
• Partial remission: improved eGFR but <60 mL/min/1.73 m² 1, 2
• Non-responders: no significant improvement 1, 2

Monitor creatinine weekly during treatment 5

Prognostic Factors

Neutrophil infiltration on biopsy predicts better complete remission rates compared to lymphocyte-only infiltrates 2

Earlier steroid initiation improves outcomes - delay in treatment correlates with worse renal recovery 7, 2

Interstitial fibrosis on biopsy indicates poorer prognosis and may warrant more aggressive or prolonged therapy 7

Critical Pitfalls to Avoid

Do not abruptly discontinue steroids even after short courses - always taper to prevent adrenal crisis 4

Do not continue nephrotoxic medications (PPIs, NSAIDs, certain antibiotics) during steroid treatment as this significantly impairs recovery 3

Do not delay biopsy excessively if diagnosis is uncertain, but steroid treatment can be initiated empirically if clinical suspicion is high and biopsy will be delayed 5

Do not use supraphysiologic pulse steroids routinely - reserve for severe cases or inability to take oral medications, as oral therapy is equally effective with fewer complications 1, 2

Avoid reflex kidney biopsy in ICI-related AIN until after steroid trial, as swift treatment of the autoimmune component is more important 5

Evidence Quality Note

Current treatment recommendations are based primarily on observational studies and small randomized trials 1, 2, with a large prospective randomized controlled trial (PRAISE) ongoing to definitively establish steroid efficacy 7. Despite limited high-quality evidence, steroids remain standard practice given the immune-mediated pathophysiology of AIN and consistent observational data showing benefit when used early.