WBR0380

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 54-year-old man presents to the emergency department complaining of fever and diffuse pruritic rash. Further questioning reveals the patient was recently prescribed trimethoprim-sulfamethoxazole (TMP-SMX) for an uncomplicated urinary tract infection. On admission, his temperature is 38.5 ᵒC (101.3 ᵒF), heart rate is 98/min, and blood pressure is 118/80 mmHg. Physical examination is significant for costovertebral angle tenderness bilaterally and a maculopapular rash predominantly involving the trunk. Work-up reveals a creatinine of 2.6 mg/dL and eosinophiluria with eosinophil casts on urinalysis. Which of the following is the most important prognostic factor in this patient’s condition?]]
Answer A	AnswerA::Duration of acute kidney injury
Answer A Explanation	AnswerAExp::The best prognostic factors in ATIN are the duration of acute renal failure and the renal function several weeks after the diagnosis.
Answer B	AnswerB::Patient age
Answer B Explanation	AnswerBExp::Generally, advanced patient age is an important factor in renal function since creatinine clearance normally declines with increasing age. However, age is not the most important factor for prognosis in ATIN.
Answer C	AnswerC::Dose of offending medication
Answer C Explanation	AnswerCExp::Development of drug-induced ATIN is not dose-related. Nonetheless, the time until discontinuing of the offending medications and delay in initiating steroid therapy are both important prognostic factors.
Answer D	AnswerD::Presence of urinary eosinophils
Answer D Explanation	[[AnswerDExp::Eosinophiluria is a common finding in drug-induced ATIN. The finding might be useful in confirming the diagnosis, although false positive and false negative rates remain relatively elevated. Eosinophiluria is not directly correlated with the outcome of the disease.]]
Answer E	AnswerE::Maximal serum creatinine levels
Answer E Explanation	AnswerEExp::Analysis of different series suggests that maximal serum creatinine levels i.e. severity of renal failure, has little prognostic value.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. The most common etiologies of ATIN include drugs such as antimicrobials, NSAIDs, and analgesics, immunologic diseases, and infections. Clinical presentation of ATIN is very variable ranging from asymptomatic renal functional decline to a syndrome that includes rash, fever, and livido reticularis. Work-up often reveals pyuria and eosinophiluria with eosinophil casts. However, non-invasive techniques have clear limitations in the diagnosis of ATIN and renal biopsy is often essential. The hallmark of ATIN on biopsy is the presence of inflammatory infiltrates within the interstitium. The mainstay of treatment of drug-induced ATIN is discontinuation of the offending medication and administration of a short course of corticosteroids in order to limit the progression to ESRD in some patients. Recovery ranges widely. Approximately 50% of patients fail to fully recover normal renal function. Several prognostic factors have been studied to determine the eventual outcome of renal function in patients with ATIN. Histologic findings such as diffuse interstitial infiltration and extensive interstitial fibrosis have been linked to poorer renal outcomes. The most important prognostic factors are the duration of acute renal failure and renal function 2-3 weeks after the diagnosis. The severity of renal failure at diagnosis is of no prognostic significance. Educational Objective: Drug-induced acute tubulointerstitial nephritis is the most common cause of acute tubulointerstitial nephritis. Antimicrobials and NSAIDs are commonly attributed to drug-induced AIN. Transformation of interstitial cellular infiltrates into fibrosis is the most important prognostic factor in determining the outcome of AIN. References: Neilson EG. Mechanisms of disease: Fibroblasts – a new look at an old problem. Nat Rev Nephrol. 2006; 2:101-107 Praga M, Gonzalez E. Acute Interstitial Nephritis. Kidney International. 2010; 77:956-961]]
Approved	Approved::Yes
Keyword	WBRKeyword::ATIN, WBRKeyword::AIN, WBRKeyword::Acute interstitial nephritis, WBRKeyword::Drug-induced nephritis, WBRKeyword::Acute tubulointerstitial nephritis
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