Renal · Acute Interstitial Nephritis
The facts most likely to be tested
Acute interstitial nephritis is most commonly caused by a hypersensitivity reaction to medications, particularly penicillins, cephalosporins, sulfonamides, NSAIDs, and proton pump inhibitors.
The classic clinical triad of fever, maculopapular rash, and arthralgias is present in fewer than 10% of patients.
Urinalysis typically reveals sterile pyuria and white blood cell casts, which are highly suggestive of an inflammatory process in the renal interstitium.
Eosinophiluria is a classic finding, though its sensitivity and specificity are low, making Wright or Hansel stain the preferred method for detection.
Patients often present with acute kidney injury characterized by a rising serum creatinine and a disproportionate increase in fractional excretion of sodium (FeNa > 2%).
The definitive diagnostic procedure is a renal biopsy, which demonstrates interstitial edema and lymphocytic infiltration of the renal tubules.
The first-line management strategy is the immediate discontinuation of the offending medication, which often leads to the resolution of renal dysfunction.
Vignette unlocked
A 54-year-old male presents to the clinic for a follow-up regarding his recent treatment for a urinary tract infection. He has been taking trimethoprim-sulfamethoxazole for the past 10 days. He reports a new diffuse maculopapular rash on his trunk and mild joint pain. Laboratory studies reveal a serum creatinine of 2.1 mg/dL, up from a baseline of 0.9 mg/dL. Urinalysis shows white blood cell casts and eosinophiluria without evidence of bacteriuria.
What is the most likely diagnosis?
Acute Interstitial Nephritis
The patient's presentation of a new rash, elevated creatinine, and sterile pyuria with WBC casts following antibiotic use is classic for drug-induced acute interstitial nephritis.
Full handout
High yield triage
Etiology / Epidemiology
Most commonly caused by drug hypersensitivity (70-90%), specifically penicillins, NSAIDs, and PPIs.
Clinical Manifestations
Classic triad of fever, rash, and eosinophilia; WBC casts on urinalysis.
Diagnosis
Renal biopsy is the gold standard; urinalysis shows sterile pyuria.
Treatment
Immediate discontinuation of offending agent; consider corticosteroids if renal function fails to improve.
Prognosis
Most recover with drug cessation; chronic kidney disease risk if diagnosis is delayed.
Full handout
Epidemiology & Etiology
AIN is an immune-mediated inflammatory process of the renal interstitium and tubules. Drug-induced causes account for the vast majority of cases. Other triggers include infections (e.g., Legionella, CMV) and autoimmune diseases (e.g., SLE, Sjögren's).
Pertinent Anatomy
The pathology is localized to the renal interstitium and tubules, sparing the glomeruli and vessels. This explains why patients typically present with tubular dysfunction rather than nephrotic-range proteinuria.
Pathophysiology
The process is a Type IV hypersensitivity reaction triggered by drug-hapten binding to tubular basement membranes. This recruits T-lymphocytes and inflammatory cells, leading to interstitial edema and tubular damage. The resulting tubular injury causes impaired concentration and electrolyte wasting.
Clinical Manifestations
Patients present with acute kidney injury, often manifesting as oliguria or rising creatinine. The classic triad of fever, maculopapular rash, and arthralgias is present in <30% of cases. Red flag: persistent elevation of creatinine despite stopping the suspected drug requires urgent evaluation.
Diagnosis
Urinalysis typically reveals sterile pyuria and WBC casts. Renal biopsy is the gold standard for definitive diagnosis, showing interstitial edema and inflammatory infiltrates. Eosinophiluria (via Hansel stain) is suggestive but lacks sufficient sensitivity/specificity for routine use.
Treatment
The primary intervention is the immediate discontinuation of the offending medication. If renal function does not improve within 3-7 days, a course of corticosteroids may be initiated to reduce inflammation. Avoid NSAIDs as they are a common cause and can exacerbate renal injury.
Prognosis
Most patients achieve full recovery of renal function upon drug withdrawal. Chronic kidney disease may develop if the inflammatory insult is prolonged, leading to irreversible interstitial fibrosis.
Differential Diagnosis
Acute Tubular Necrosis: muddy brown casts
Glomerulonephritis: RBC casts and hematuria
Pyelonephritis: positive urine culture and systemic infection signs
Prerenal Azotemia: BUN/Cr ratio >20:1
Drug-induced ATN: usually associated with aminoglycosides or contrast