What is the most likely cause of impaired renal function in a patient with rheumatoid arthritis on hydroxychloroquine, who showed significant improvement with cefuroxime (Cefuroxime, a second-generation cephalosporin antibiotic) but subsequently developed deteriorating renal function?

Acute Interstitial Nephritis (AIN) from Cefuroxime

The most likely cause of kidney function deterioration in this patient is acute interstitial nephritis (AIN) induced by cefuroxime (Answer B). This diagnosis is strongly supported by the temporal relationship between antibiotic exposure and renal deterioration, the clinical improvement from pneumonia indicating the drug is no longer needed for its therapeutic effect, and the well-documented nephrotoxic potential of cephalosporins.

Clinical Reasoning

The key diagnostic feature is the timing of renal deterioration occurring after clinical improvement from pneumonia while continuing cefuroxime therapy. 1 The FDA label for cefuroxime explicitly warns that "nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporins," and emphasizes that "high and prolonged serum antibiotic concentrations can occur" even from usual doses. 1

Why AIN is Most Likely

• Drug-induced AIN accounts for 70% of all AIN cases, with antibiotics causing 49% of drug-induced cases. 2 Among antibiotics, cephalosporins are well-recognized causes of AIN. 3, 4

• Cefuroxime specifically has documented cases of causing acute interstitial nephritis. 4 One case report demonstrated DIAN (drug-induced allergic nephritis) with cefuroxime where renal deterioration occurred during exposure and improved upon discontinuation, with the pattern repeating upon rechallenge. 4

• The absence of typical allergic symptoms does not exclude AIN. 4 Patients with PPI-induced AIN were noted to be "less symptomatic" than those with antibiotic-induced or NSAID-induced AIN, indicating that drug-induced AIN can present without classic hypersensitivity features. 2

• The clinical scenario fits the typical pattern: improvement of the primary infection followed by renal deterioration while continuing the antibiotic. 2 This temporal relationship is the hallmark of drug-induced AIN.

Why Other Options Are Less Likely

Renal vasculitis (Option A) is unlikely because:

• While rheumatoid arthritis can cause renal vasculitis, the temporal relationship with cefuroxime exposure is more compelling. 5
• Vasculitis would typically present with other systemic features or urinary findings (red cell casts, significant hematuria) not mentioned in this case. 5

Prerenal acute kidney failure (Option C) is unlikely because:

• The patient showed "significant improvement" from pneumonia, suggesting adequate hydration and hemodynamic stability. 6
• Prerenal azotemia would be expected to improve with fluid resuscitation, not deteriorate despite clinical improvement. 6

Immune complex glomerulonephritis (Option D) is unlikely because:

• This would typically present with nephritic or nephrotic features. 6
• The temporal relationship with drug exposure is more consistent with AIN. 2

Management Implications

Immediate discontinuation of cefuroxime is the most critical intervention. 2, 4 The duration of drug exposure correlates with recovery outcomes: complete recovery occurred with 15 days of exposure versus no recovery with 130 days of exposure (P = 0.04). 2

Consider corticosteroid therapy if renal function does not improve after drug discontinuation. 2 However, delays in starting steroid therapy adversely affect recovery (8 days for complete recovery vs 35 days for no recovery, P = 0.05). 2

Switch to an alternative antibiotic if continued treatment is needed. 3 In a similar case of cephalosporin-induced AIN, switching to ciprofloxacin allowed completion of therapy while renal function improved. 3

Common Pitfalls

• Do not assume normal baseline renal function excludes drug-induced nephrotoxicity. 1 The FDA label warns that cephalosporins should be given with caution even in patients without pre-existing renal disease. 1

• Do not delay kidney biopsy if the diagnosis is uncertain or if steroid therapy is being considered. 2 While biopsy is the gold standard, delays in obtaining it correlate with worse outcomes. 2

• Do not continue the offending drug while "monitoring" renal function. 4 Failure to recognize and discontinue the causative agent may result in irreversible renal failure. 4