The selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) cause renal syndromes that parallel those of the traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Celecoxib promotes haemodynamic acute renal failure (ARF) via inhibition of vasodilatory prostaglandins synthesized by the COX-2 enzyme [1,2]. Another potential cause of ARF associated with celecoxib is acute tubulointerstitial nephritis (ATIN).
A 34-year-old male with HIV infection presented complaining of weakness, anorexia and decreased urine out-put. Medications included lamivudine 150 mg bid, lopinavir 3 mg bid, tenofovir 300 mg qd and prevacid 30 mg qd. The patient was on a stable regimen of these drugs for 10 months. Celecoxib 200 mg bid was added 3 weeks prior to admission. Serum creatinine concentration measured 5 weeks prior to celecoxib therapy was at baseline (114 µmol/l).
Physical examination revealed a blood pressure of 115/70 mmHg and pulse of 85/min without orthostasis. The rest of the exam was benign. Laboratory data demonstrated blood urea nitrogen (16.4 mmol/l) and serum creatinine (292 µmol/l). Urinalysis had 2+ protein on dipstick, while the urine sediment contained a few granular casts, 35 red blood cells and 46 white blood cells/high power field. Ultrasound revealed large echogenic kidneys.
The patient received i.v. normal saline (2 l). Celecoxib and antiretroviral medications were discontinued. Renal function worsened over the next 3 days; creatinine increased to 521.6 µmol/l. Renal biopsy demonstrated a diffuse interstitial infiltrate with lympocytes, eosinophils, marked tubulitis and interstitial oedema. The glomeruli and vessels were unremarkable. Oral prednisone 60 mg/day for 2 weeks was administered. Serum creatinine declined from 521 to 106 µmol/l over the next 3 weeks.
ARF, hyperkalaemia, hyponatraemia, oedema formation and hypertension have all been noted with the selective COX-2 inhibitors [1,2]. Haemodynamic ARF develops in patients treated with NSAIDs who depend on vasodilatory prostaglandins to maintain blood flow and glomerular filtration. Based on this known effect, celecoxib-associated inhibition of vasodilatory prostaglandins was considered as a possible cause of haemodynamic ARF in this patient. However, despite discontinuation of celecoxib and volume repletion, renal function continued to deteriorate making haemodynamic ARF unlikely.
The temporal association of celecoxib administration and development of ATIN suggests that this drug was the culprit. Like traditional NSAIDs, ATIN complicates ther-apy with this new class of drugs (Table 1). Since these drugs block COX, arachidonic acid may be shunted into the lipoxygenase pathway, favouring production of proinflammatory leukotrienes. This may promote the development of ATIN.
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Conflict of interest statement. None declared.
1Yale University School of Medicine 2Section of Nephrology Yale University School of Medicine New Haven USA Email: mark.perazella{at}yale.edu
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