Reversal of refractory sulfasalazine-related renal failure after treatment with corticosteroids

Background: Sulfasalazine is a combination of sulfapyridine and 5-aminosalicylic acid and is used as a first-line treatment in inflammatory bowel disease.

Objective: We describe a case of acute interstitial nephritis that presented after 7 months of sulfasalazine therapy. Despite the discontinuation of the drug, the patient's renal function continued to deteriorate and recovered only when systemic corticosteroid treatment was initiated.

Case summary: A 19-year-old white male (weight, 65 kg) presented in November 2006 with upper abdominal pain, fever ≥38°C, bloody diarrhea, anorexia, and weight loss. Ulcerative colitis involving the left colon was diagnosed based on results of a colonoscopy and intestinal biopsy, and treatment was initiated with cefprozil 1 g/d, mesalamine 3 g/d, methylprednisolone 32 mg/d, and ranitidine 300 mg/d. All drugs were administered orally. Cefprozil and ranitidine were discontinued after 10 days. Mesalamine was discontinued 1 month later because of gastrointestinal adverse effects (vomiting and diarrhea), and methylprednisolone was tapered over the next 3 months to zero. The patient then had a relapse, and sulfasalazine 2 g/d orally was administered. Seven months after the initiation of sulfasalazine, the patient developed fatigue, nausea, fever more prominent in the afternoon (increased from 38°C to 40°C), and nocturia, and he was admitted to the hospital. He had no history of renal impairment. Laboratory test results showed elevated serum urea and creatinine levels (170 and 7 mg/dL, respectively), while kidney ultrasound showed normal kidneys without obstruction. The patient had a Naranjo Adverse Drug Reaction Probability scale score of 6, indicating a probable adverse drug reaction with sulfasalazine. Based on these findings, sulfasalazine-related nephrotoxicity was suspected, and the drug was discontinued. During the next 4 days, serum urea and creatinine values increased to 212 and 8.3 mg/dL, respectively, and then remained stable for 3 days. A renal biopsy was performed, which revealed changes compatible with granulomatous interstitial nephritis. The patient received methylprednisolone 500 mg IV for 3 days, followed by oral administration of methylprednisolone 16 mg/d for 1 month. Renal function recovered completely a few days after initiation of corticosteroids, and the patient's condition continued to be stable 1 year later (eg, serum urea, 34 mg/dL; creatinine level, 0.9 mg/dL).

Conclusions: Although this isolated case of sulfasalazine- related interstitial nephritis cannot lead to definite conclusions, treatment with corticosteroids was effective in this patient and should be considered irrespective of the time of exposure to sulfasalazine. However, randomized controlled trials are needed to provide evidence regarding the efficacy and tolerability profile of corticosteroids.