NDT Advance Access originally published online on October 4, 2005
Nephrology Dialysis Transplantation 2006 21(1):237-238; doi:10.1093/ndt/gfi178
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Fluoroquinolone-induced acute interstitial nephritis in immunocompromised patients: two case reports
Email: chenhc{at}kmu.edu.twSir,
Nephrotoxic side effects related to the use of fluoroquinolones (FQ) are relatively rare, and only four cases were reported with the newer fluoroquinolones (levofloxacin and norfloxacin) [1]. The risk factors and mechanisms were largely unknown. We described two biopsy-proven cases of levofloxacin and ciprofloxacin induced acute interstitial nephritis (AIN) in immunocompromised patients.
Case 1. A 41-year-old Chinese female with known history of systemic lupus erythematosus was treated with levofloxacin 200 mg twice a day for 10 days because of urinary tract infection. At the first presentation, biochemical tests were normal except lymphopenia (lymphocyte count, 1067/µl) which had been noted for 2 years. Urinalysis demonstrated WBC 25–50 per high-power field (hpf) and bacteriuria. However, fever developed after 1 week of levofloxacin treatment. Physical examination revealed excessive extracellular fluid volume. Laboratory studies showed serum creatinine 5.4 mg/dl, serum urea nitrogen (BUN) 27 mg/dl, WBC count 8610/µl with 60.4% neutrophils, 22.9% lymphocytes and 2.4% eosinophils. Urinalysis revealed WBC 2–5/hpf without bacteria. Immunoglobulin, complement and ANA were all normal. A renal biopsy showed normal glomeruli with mild hypercellularity, interstitial infiltration with mononuclear cells, no immunofluorescent expression, and no electron dense deposits. A diagnosis of AIN was made. Serum creatinine decreased to 1.08 mg/dl 10 days after admission. She was discharged uneventfully.
Case 2. A 74-year-old Chinese male was admitted to our hospital because of high fever. At that time, serum creatinine was 1.4 mg/dl and WBC count was 1350/dl with 8% neutrophils and 62% lymphocytes. Intravenous cefepime 2 g per 12 h were used for neutropenic fever. Blood culture revealed Pseudomonas aeruginosa bacteraemia. After fever subsided, antibiotics were shifted to oral ciprofloxacin 500 mg twice a day on day 7. However, nausea and vomiting developed 4 days after ciprofloxacin treatment. Physical examination revealed tachypnea. Laboratory studies were serum creatinine 6.4 mg/dl, BUN 57 mg/dl, WBC count 8220/µl with 75.2% neutrophils, 19.3% lymphocytes and no eosinophils. Urinalysis revealed WBC 5–10/hpf and RBC 10–25/hpf with WBC casts. Because of oliguria and uraemic symptoms, haemodialysis was performed on day 16 when peak serum creatinine was 11.4 mg/dl. Renal biopsy demonstrated normal glomeruli, interstitial infiltration with mononuclear cells, negative immunofluorescent expression, and no electron dense deposits. A diagnosis of AIN was established. Three haemodialyses were conducted. Serum creatinine decreased to 1.4 mg/dl on day 37. He was discharged uneventfully.
Comment. The incidence of elevated serum creatinine levels related to FQ range from 0.2 to 1.3% [2]. However, levofloxacin-induced AIN is relatively rare. One case of biopsy-proven granulomatous interstitial nephritis and another case of clinically suspected AIN with purpura had been reported [3,4].
Neutropenia and lymphopenia as presented in our two cases might be risk factors of FQ-induced nephrotoxicity. Cancer patients, combined nephrotoxic agents, ciprofloxacin and old age (>50 years) were observed more commonly in the reported cases of FQ-induced nephrotoxicity as proposed by Lomaestro [1]. Several reported cases showed that cancer patients especially during neutropenic fever period after chemotherapy might undergo FQ-induced AIN [5]. On the other hand, lymphopenia was also observed in FQ-induced AIN in one reported case and our first case [3]. Cell mediated hypersensitivity was supposed in FQ-induced AIN [1]. Ciprofloxacin could modulate immune system and induce the expression of interleukin-2 and interferon-gamma in human T-lymphocytes [6]. We propose that sensitized lymphocytes expanding quickly by FQ-induced cytokine reaction during the recovery of leukopenia result in FQ-induced AIN.
In summary, both older and newer fluoroquinolones, ciprofloxacin and levofloxacin, could cause acute interstitial nephritis or oliguric acute renal failure that requires haemodialysis. Clinicians should be aware of these adverse effects especially in neutropenic and lymphopenic patients.
Conflict of interest statement. None declared.
Division of Nephrology Department of Internal Medicine Kaohsiung Medical University Kaohsiung Taiwan
References
- Lomaestro BM. Fluoroquinolone-induced renal failure. Drug Saf 2000; 22: 479–485[CrossRef][Web of Science][Medline]
- Wolfson JS, Hooper DC. Overview of fluoroquinolone safety. Am J Med 1991; 91: 153S–161S[CrossRef][Medline]
- Famularo G, De SC. Nephrotoxicity and purpura associated with levofloxacin. Ann Pharmacother 2002; 36: 1380–1382[Abstract]
- Ramalakshmi S, Bastacky S, Johnson JP. Levofloxacin-induced granulomatous interstitial nephritis. Am J Kidney Dis 2003; 41: E7[CrossRef][Medline]
- Lo WK, Rolston KV, Rubenstein EB, Bodey GP. Ciprofloxacin-induced nephrotoxicity in patients with cancer. Arch Intern Med 1993; 153: 1258–1262
[Abstract/Free Full Text] - Riesbeck K. Immunomodulating activity of quinolones: review. J Chemother 2002; 14: 3–12[Web of Science][Medline]
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