In a 35-year-old woman with rheumatoid arthritis on hydroxychloroquine who develops community-acquired pneumonia treated with cefuroxime and then experiences new-onset renal dysfunction, what is the most likely cause of the kidney injury?

Acute Interstitial Nephritis from Cefuroxime

The most likely cause of kidney function deterioration in this patient is acute interstitial nephritis (AIN) secondary to cefuroxime therapy (Answer B). This represents a classic drug-induced hypersensitivity reaction occurring after antibiotic exposure in the setting of acute infection treatment.

Clinical Reasoning

Why Acute Interstitial Nephritis is Most Likely

Drug-induced AIN is the most common etiology of AIN, accounting for 60-70% of all cases, with antimicrobials being among the most frequent offending agents 1, 2. The temporal relationship is critical here: the patient's renal function was initially normal, she received cefuroxime for pneumonia with clinical improvement, and subsequently developed renal dysfunction—this sequence strongly implicates the antibiotic as the causative agent 3, 4.

Cephalosporins, including cefuroxime, are well-documented causes of interstitial nephritis 5. The FDA label for cefuroxime specifically lists interstitial nephritis as a rare but recognized adverse reaction 5. The timing of onset (typically days to weeks after drug initiation) fits this clinical scenario 2.

Key Distinguishing Features

• Drug-induced AIN accounts for 15-27% of acute kidney injury cases requiring renal biopsy 2
• The classic triad of fever, rash, and arthralgias is absent in up to two-thirds of patients with AIN, making diagnosis challenging based on clinical features alone 3, 4
• The patient's normal baseline renal and liver function, followed by deterioration after antibiotic exposure, creates a clear temporal association 1, 2

Why Other Options Are Less Likely

Renal Vasculitis (Option A) - Unlikely

Renal vasculitis would typically present with:

• Rapidly progressive glomerulonephritis with active urinary sediment (dysmorphic RBCs, RBC casts) 6
• Positive ANCA serology (MPO-ANCA or PR3-ANCA) or other vasculitis markers 6
• Systemic manifestations beyond isolated pneumonia 6
• The patient's rheumatoid arthritis on hydroxychloroquine alone does not increase vasculitis risk sufficiently to make this the primary consideration 6

Prerenal Acute Kidney Failure (Option C) - Unlikely

Prerenal AKI would require:

• Evidence of volume depletion, hypotension, or decreased effective circulating volume 7, 8
• The patient showed "significant improvement" with cefuroxime treatment, suggesting adequate hydration and perfusion 7
• Prerenal AKI typically improves with fluid resuscitation and would not worsen after clinical improvement from pneumonia 7, 8

Immune Complex Glomerulonephritis (Option D) - Unlikely

This would manifest with:

• Proteinuria, hematuria, and nephritic or nephrotic features 6
• Complement abnormalities or other serologic markers 6
• While rheumatoid arthritis patients can develop glomerulonephritis, the temporal relationship with antibiotic exposure makes drug-induced AIN far more likely 6

Diagnostic Approach

Clinical Assessment

• History of new medication exposure (cefuroxime) is the most important diagnostic clue 3, 1
• Look for fever, rash, arthralgias, but remember these are present in only one-third of cases 3, 4
• Timing: AIN typically develops days to weeks after drug initiation 2

Laboratory Evaluation

• Urinalysis may show sterile pyuria, white blood cell casts, and mild proteinuria (typically <1-2g/day) 3, 4
• Urine eosinophils have limited diagnostic utility with poor sensitivity and specificity 3, 4
• Peripheral eosinophilia is present in only a minority of cases 3, 2
• Serum creatinine elevation without other clear etiology 1, 2

Definitive Diagnosis

• Renal biopsy remains the gold standard for diagnosis, showing interstitial inflammation with lymphocytes, macrophages, eosinophils, and plasma cells 3, 1, 2
• Biopsy may not be required in mild cases or when clinical improvement is rapid after drug discontinuation 3

Management Recommendations

Immediate Actions

• Discontinue cefuroxime immediately—this is the mainstay of therapy 3, 1, 2
• Switch to an alternative antibiotic from a different class to complete pneumonia treatment 6, 7
• Review all medications for other potential nephrotoxins and discontinue non-essential agents 6, 7

Corticosteroid Therapy

• Early corticosteroid administration (within 7 days of diagnosis) improves recovery of renal function and decreases risk of chronic kidney disease 2
• Prednisone 1 mg/kg/day is the typical regimen, though evidence comes from observational studies rather than randomized trials 3, 1, 2
• Delayed steroid treatment after interstitial fibrosis develops has less therapeutic benefit 2

Monitoring

• Serial serum creatinine and electrolytes to assess response 1, 2
• Urinalysis to monitor resolution of inflammatory markers 4
• The time until removal of the offending agent provides the best prognostic information for return to baseline renal function 3, 2

Common Pitfalls to Avoid

• Do not assume AIN is absent because the classic triad (fever, rash, arthralgias) is missing—this occurs in two-thirds of cases 3, 4
• Do not rely on urine eosinophils as a definitive test—they have poor diagnostic accuracy 3, 4
• Do not delay discontinuation of the offending drug while awaiting biopsy confirmation in obvious cases 3, 1
• Do not attribute worsening renal function to prerenal causes when the patient is clinically improving from their infection 7, 8
• Do not delay corticosteroid therapy beyond 7 days if AIN is strongly suspected, as this worsens long-term outcomes 2

Prognosis

• The prognosis for drug-induced AIN is generally good, with at least partial recovery of kidney function normally observed 1
• Early recognition and drug discontinuation are crucial to prevent progression to chronic kidney disease 1, 2
• Patients can develop permanent renal impairment if diagnosis and treatment are delayed 1, 2