Nephrology Department, General Hospital of Rhodes, Rhodes, Greece.
Clin Ther. 2010 Oct;32(11):1906-10. doi: 10.1016/j.clinthera.2010.10.002.
Sulfasalazine is a combination of sulfapyridine and 5-aminosalicylic acid and is used as a first-line treatment in inflammatory bowel disease.
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.
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).
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.
柳氮磺胺吡啶是磺胺吡啶和 5-氨基水杨酸的复方制剂，用于治疗炎症性肠病的一线药物。
我们描述了一例柳氮磺胺吡啶治疗 7 个月后发生的急性间质性肾炎。尽管停止了药物治疗，但患者的肾功能仍持续恶化，仅在开始全身皮质类固醇治疗后才恢复。
一名 19 岁白人男性（体重 65kg）于 2006 年 11 月因上腹痛、发热≥38°C、血性腹泻、食欲不振和体重减轻就诊。根据结肠镜检查和肠活检结果诊断为溃疡性结肠炎，累及左结肠，给予头孢丙烯 1g/d、美沙拉嗪 3g/d、甲泼尼龙 32mg/d 和雷尼替丁 300mg/d 口服治疗。所有药物均口服给药。头孢丙烯和雷尼替丁在 10 天后停用。由于胃肠道不良反应（呕吐和腹泻），美沙拉嗪在 1 个月后停用，甲泼尼龙在接下来的 3 个月内逐渐减量至零。患者随后复发，给予柳氮磺胺吡啶 2g/d 口服治疗。柳氮磺胺吡啶治疗开始后 7 个月，患者出现疲劳、恶心、午后发热更明显（从 38°C 升高至 40°C）和夜尿，并住院。他没有肾功能损害的病史。实验室检查结果显示血清尿素和肌酐水平升高（分别为 170 和 7mg/dL），而肾脏超声显示肾脏无梗阻。患者的 Naranjo 药物不良反应概率量表评分为 6，提示与柳氮磺胺吡啶相关的药物不良反应可能性较大。根据这些发现，怀疑与柳氮磺胺吡啶相关的肾毒性，并停止了该药物的使用。在接下来的 4 天里，血清尿素和肌酐值分别升高至 212 和 8.3mg/dL，然后稳定了 3 天。进行了肾活检，显示符合肉芽肿性间质性肾炎的改变。患者接受了 3 天的甲基强的松龙 500mg IV 治疗，随后口服甲泼尼龙 16mg/d 1 个月。皮质类固醇治疗开始后几天内肾功能完全恢复，1 年后患者病情继续稳定（例如，血清尿素 34mg/dL；肌酐水平 0.9mg/dL）。
尽管这例孤立的柳氮磺胺吡啶相关性间质性肾炎不能得出明确的结论，但皮质类固醇治疗对该患者有效，无论接触柳氮磺胺吡啶的时间如何，都应考虑使用。然而，需要进行随机对照试验以提供关于皮质类固醇疗效和耐受性的证据。
