Fever, maculopapular rash, and acute renal failure (eg, elevated creatinine, oliguria) occurring within a few weeks of starting a beta-lactam antibiotic are highly suggestive of drug-induced acute interstitial nephritis (AIN).  Other commonly implicated medications include nonsteroidal anti-inflammatory drugs, sulfonamides, rifampin, proton pump inhibitors, and diuretics.  Many patients have increased levels of serum eosinophils and eosinophiluria (detected by Hansel or Wright stain).  Urinalysis may also show white blood cells, white blood cell casts, and red blood cells.  Symptoms most commonly occur 1-3 weeks after drug initiation and typically resolve with cessation of the offending medication.

AIN is thought to be due to IgE-mediated (type I) or cell-mediated (type IV) hypersensitivity.  It primarily involves the renal interstitium, causing interstitial edema and leukocyte infiltration (particularly lymphocytes, macrophages, and eosinophils).  Inflammatory cells commonly infiltrate the tubular epithelium (tubulitis) and granuloma formation may be observed.

(Choice A)  Calyces and ureters are most commonly involved in nephrolithiasis and associated hydronephrosis, which can cause hematuria and renal failure.  However, nephrolithiasis typically causes flank pain; fever, rash, and eosinophiluria would be unexpected.

(Choice B)  Glomeruli are involved in poststreptococcal glomerulonephritis, which can cause acute kidney injury 1-3 weeks after infection with group A beta-hemolytic streptococcus.  However, dysmorphic red blood cells and/or red blood cell casts would be expected in a nephritic disease; eosinophiluria, fever, and rash are more consistent with AIN.

(Choice D)  Pathology affecting the renal papillae (papillary necrosis) is common in severe, acute pyelonephritis and in patients with sickle cell disease, diabetes mellitus, or analgesic nephropathy.  Urinalysis shows hematuria or sterile pyuria, but rash and eosinophiluria are unexpected.

(Choice E)  Small renal arterioles are not involved in AIN.  They are most commonly damaged in hypertensive or diabetic nephropathy, which typically presents with proteinuria, not with pyuria and urinary eosinophils.

Educational objective:
Fever, maculopapular rash, and acute renal failure occurring 1-3 weeks after beginning a new medication (eg, antibiotics, proton pump inhibitors) is highly suggestive of acute interstitial nephritis.  Peripheral eosinophilia, sterile pyuria, eosinophiluria, and white blood cell casts may also be seen.  Histology reveals leukocyte infiltration and edema of the renal interstitium.