What is the treatment for a 51-year-old female patient with impaired renal function (creatinine level of 7), biopsy-confirmed acute and chronic interstitial nephritis with lymphocytic and plasma cell infiltration, few eosinophils, and moderate fibrosis?

Treatment of Acute and Chronic Interstitial Nephritis with Severe Renal Impairment

For this 51-year-old woman with biopsy-proven acute and chronic interstitial nephritis, creatinine of 7, and moderate fibrosis, the primary treatment is immediate identification and discontinuation of any causative drug, followed by corticosteroid therapy (prednisone 0.5-1 mg/kg/day) if renal function does not improve within 3-5 days of drug cessation. 1, 2

Immediate Diagnostic and Therapeutic Steps

Identify and Remove the Culprit Agent

• Systematically review all medications, particularly focusing on:
  • Proton pump inhibitors (PPIs) - now the second most common cause of drug-induced AIN at 14% of cases 3
  • Antibiotics (49% of drug-induced AIN cases) 3
  • NSAIDs (11% of cases) 3
• Discontinue the offending agent immediately - this is the cornerstone of therapy and delays in discontinuation directly correlate with poor recovery 1, 3, 2

Exclude Other Reversible Causes

Before initiating immunosuppression, mandatory exclusions include: 1

• Hypovolemia and dehydration
• Urinary tract obstruction
• Recent IV contrast exposure
• Urinary tract infection
• Medication-induced acute tubular necrosis
• Hypotension or hypertensive emergency

Corticosteroid Therapy Algorithm

Indications for Steroid Initiation

Begin corticosteroids if renal function fails to improve 3-5 days after discontinuing the causative agent. 2 Given this patient's creatinine of 7 with moderate fibrosis, immediate steroid therapy is warranted alongside drug discontinuation. 1

Dosing Regimen Based on Severity

For Grade 3 severity (creatinine ≥3× baseline or ≥4.0 mg/dL): 1

• IV methylprednisolone 1-2 mg/kg daily initially
• Transition to oral prednisone 0.5-1 mg/kg/day after clinical stabilization 1, 4
• Continue high-dose therapy for minimum 4 weeks 5
• Taper slowly over 6 months after achieving response 5

Alternative oral regimen:

• Prednisone 1 mg/kg/day (typically 60 mg daily for average adult) 6, 2
• Maintain for 4-6 weeks, then taper gradually 2

Critical Prognostic Factors Affecting Recovery

Poor Prognostic Indicators Present in This Case

The presence of moderate fibrosis is particularly concerning and indicates: 1, 3

• Chronic component to the injury
• Reduced likelihood of complete recovery
• Need for aggressive early intervention

Duration of drug exposure and delay in steroid initiation are the strongest predictors of incomplete recovery: 1, 3

• Complete recovery: mean 15 days drug exposure, 8 days to steroid initiation
• Partial recovery: mean 30 days drug exposure, 11 days to steroid initiation
• No recovery: mean 130 days drug exposure, 35 days to steroid initiation 3

Expected Outcomes with Treatment

At 6 months post-diagnosis for drug-induced AIN treated with steroids: 1, 3

• 49% achieve complete recovery (creatinine within 25% of baseline or <1.4 mg/dL)
• 39% achieve partial recovery (≥50% decrease from peak creatinine)
• 12% have no recovery (<50% decrease from peak creatinine)

Management of Steroid-Resistant Disease

Second-Line Therapy: Mycophenolate Mofetil

If renal function fails to improve or worsens despite 4-6 weeks of corticosteroid therapy, add mycophenolate mofetil (MMF). 6

MMF dosing: 6

• 1000-1500 mg twice daily
• Well-tolerated in AIN patients
• Mean decline in creatinine from 2.3 to 1.6 mg/dL over 24 months in steroid-resistant cases 6
• Can be used as first-line therapy in patients with contraindications to corticosteroids 6

When to Consider MMF as First-Line

Consider MMF instead of corticosteroids for patients with: 5, 6

• Uncontrolled diabetes
• Severe osteoporosis
• Psychiatric conditions
• Morbid obesity
• Active infections

Monitoring and Supportive Care

Laboratory Surveillance

• Serial creatinine monitoring every 2-3 days initially, then weekly 1, 4
• Urinalysis with microscopy 1
• Urine protein-to-creatinine ratio if proteinuria present 1

Supportive Measures

• Fluid balance management - careful monitoring to avoid volume overload 1
• Renal replacement therapy if uremic symptoms develop or volume overload becomes refractory 1
• Infection prophylaxis during immunosuppression (consider trimethoprim-sulfamethoxazole) 7

Critical Pitfalls to Avoid

Common Errors Leading to Poor Outcomes

• Delaying kidney biopsy - PPI-induced AIN has particularly long delays (median exposure >30 days) and worse outcomes 3
• Continuing the offending drug - even a few extra days significantly worsens prognosis 3, 2
• Waiting too long to start steroids - delays beyond 2 weeks after drug cessation reduce recovery rates 3, 2
• Premature steroid discontinuation - taper must be gradual over 6 months to prevent relapse 5

Special Consideration for Chronic Component

The moderate fibrosis on biopsy indicates irreversible damage is already present. 1 This means:

• Complete recovery to baseline renal function is unlikely
• Goal is to preserve remaining viable nephrons
• Early aggressive treatment is critical to prevent further fibrosis progression 2

Realistic Expectations for This Patient

Given the creatinine of 7 and moderate fibrosis, this patient likely has: 1, 3

• Mixed acute and chronic injury
• Best-case scenario: Partial recovery with residual CKD stage 3-4
• Realistic goal: Stabilization of renal function and avoidance of dialysis dependence
• Treatment urgency: Immediate intervention is critical as further delays will result in permanent dialysis dependence