A 65-year-old man comes to the office with a 2-day history of skin rash and low-grade fever. He has had no cough, shortness of breath, chest pain, vomiting, dysuria, or urinary frequency. The patient was recently diagnosed with acute gouty arthritis and has been taking indomethacin for the past 10 days. Temperature is 38.1 C (100.6 F), blood pressure is 130/90 mm Hg, and pulse is 86/min. Examination shows a diffuse, maculopapular skin rash. Mucosal surfaces are moist without any lesions. Cardiopulmonary examination shows no abnormities. There is no costovertebral angle tenderness. Serum creatinine is 2.3 mg/dL (baseline 1.1 mg/dL, 2 weeks ago). Urinalysis shows numerous white blood cells/hpf. Which of the following is the most likely cause of this patient's acute renal dysfunction?
Acute interstitial nephritis | |
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NSAIDs = nonsteroidal anti-inflammatory drugs; WBC = white blood cell. | |
This patient has a rash, fever, acute kidney injury, and pyuria following the introduction of indomethacin, which is consistent with acute interstitial nephritis (AIN). AIN is a common cause of renal dysfunction and is characterized by an inflammatory infiltration of the renal interstitium, likely due to IgE- and T-cell–mediated hypersensitivity reactions.
Up to 75% of AIN cases are due to medications, particularly nonsteroidal anti-inflammatory drugs (eg, indomethacin), antibiotics (eg, penicillins, rifampin), diuretics, and proton pump inhibitors. Clinical features of AIN resemble an allergic response and include fever, rash, and eosinophilia. Urinalysis typically demonstrates sterile pyuria; white blood cell casts, hematuria, and mild proteinuria may also be seen. The presence of urine eosinophils is a supportive but nonspecific finding as eosinophiluria can occur in other diseases (eg, transplant rejection, prostatitis). Symptoms typically resolve with withdrawal of the offending agent.
(Choice B) Pyelonephritis can cause pyuria and fever, but patients typically have dysuria, flank pain, costovertebral tenderness, and symptoms of systemic toxicity (eg, nausea, vomiting, hypotension). In addition, rash would be unexpected.
(Choice C) Acute tubular necrosis is often caused by ischemic (eg, hypotension) or toxic (eg, radiocontrast) injury to the renal tubular cells. Urinalysis typically demonstrates muddy brown, granular casts, not pyuria.
(Choice D) Stevens-Johnson syndrome can cause fever and rash after initiation of a new medication; however, the rash is typically painful, macular, and progressive, with bullae formation and sloughing of the skin. Mucosal surfaces (ie, oral, ocular) are typically involved.
(Choice E) Acute uric acid nephropathy (due to crystallization of uric acid within the renal tubules) typically occurs in patients with tumor lysis syndrome, which often occurs in leukemia and lymphomas (particularly during chemotherapy). Uric acid crystals are typically seen on urinalysis, and rash would be unexpected.
Educational objective:
Acute interstitial nephritis is a common cause of renal dysfunction; up to 75% of cases are due to medications including nonsteroidal anti-inflammatory drugs, antibiotics, diuretics, and proton pump inhibitors. Presenting features include fever, rash, and eosinophilia. Urinalysis often demonstrates pyuria and white blood cell casts with elevated urine eosinophils.