Updated: 8/14/2019

Acute Interstitial Nephritis

Topic
Review Topic
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Questions
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Evidence
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Snapshot
  • TINA 60-year-old man presents to the emergency room with a 1-day history of fever and a new skin rash. He is taking methicillin for a soft tissue infection. On physical exam, he has costovetebral tenderness, and a diffuse maculopapular rash over his trunk. His serum creatinine is elevated at 3 mg/dL. Urinalysis reveals white blood cells. Further testing with Wright stain is positive for eosinophils in the urine.
Introduction
  • Clinical definition
    • acute interstitial nephritis (AIN), also known as tubulointerstitial nephritis, is an acute immune-mediated interstitial inflammation of the kidneys
  • Epidemiology
    • demographics
      • middle-aged adults
  • Etiology
    • drug-induced hypersensitivity (majority of cases)
      • typically developed between 1 week to 9 months
      • 5 Ps
        • Pee (diuretics, especially sulfa ones)
        • Pain-free (NSAIDs)
        • Penicillins and cephalosporins
        • Proton pump inhibitors
        • rifamPin
    • systemic infections
    • autoimmune diseases
      • systemic lupus erythematosus
      • sarcoidosis
  • Pathogenesis
    • type IV hypersensitivity reaction
    • T-cell-mediated attack on tubular cells
  • Prognosis
    • typically resolves after withdrawal of inciting agent
Presentation
  • Symptoms
    • primary symptoms
      • fever
      • hematuria
      • arthralgia
      • can be asymptomatic
  • Physical exam
    • rash
      • maculopapular
    • flank/costovertebral angle tenderness
Studies
  • Labs 
    • serum eosinophilia
    • elevated serum creatinine
  • Urinalysis with microscopy and sediment analysis
    • white blood cell casts 
    • hematuria
    • eosinophiluria
      • seen with Hansel or Wright stain
  • Renal biopsy
    • not usually indicated
  • Histology
    • severe tubular damage
    • interstitial edema
    • T-cell and eosinophilic infiltration
  • Diagnostic criteria
    • elevated creatinine
    • urinalysis with white cell casts and eosinophiluria
Differential
  • Acute tubular necrosis from NSAIDs
    • no rash or eosinophils
  • Renal atheroemboli
    • also presents with eosinophiluria, eosinophilia, and skin rash
    • rash is typically livedo reticularis with digital infarcts and not maculopapular
Treatment
  • Conservative
    • discontinue inciting drug
      • indications
        • for all drug-induced hypersensitivity cases
  • Medical
    • glucocorticoids      
      • indications
        • if creatinine continues to rise after stopping drugs
Complications
  • Renal failure requiring dialysis
 
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.RL.65) A 60-year-old man with a history of osteoarthritis has been awaiting hip replacement surgery for 3 years. During his annual physical, he reports that he has been taking over the counter pain medications, but that no amount of analgesics can relieve his constant pain. Laboratory results reveal that his renal function has deteriorated when compared to his last office visit 2 years ago. Serum creatinine is 2.0 mg/dL, and urinalysis shows 1+ proteinuria. There are no abnormalities seen on microscopy of the urine. A renal biopsy shows eosinophilic infiltration and diffuse parenchymal inflammation. What is the most likely explanation for this patient's deterioration in renal function? Review Topic

QID: 101019
1

Focal segmental glomerulosclerosis

9%

(5/54)

2

Ischemic acute tubular necrosis

2%

(1/54)

3

Nephrotoxic acute tubular necrosis

26%

(14/54)

4

Toxic tubulointerstitial nephritis

46%

(25/54)

5

Rapidly progressive glomerulonephritis

11%

(6/54)

M1

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PREFERRED RESPONSE 4

(M1.RL.50) A 26-year-old male currently undergoing standard therapy for a recently diagnosed active tuberculosis infection develops sudden onset of fever and oliguria. Laboratory evaluations demonstrate high levels of eosinophils in both the blood and urine. Which of the following is most likely responsible for the patient’s symptoms: Review Topic

QID: 101268
1

Rifampin

65%

(13/20)

2

Isoniazid

20%

(4/20)

3

Pyrazinamide

5%

(1/20)

4

Ethambutol

0%

(0/20)

5

Return of active tuberculosis symptoms secondary to patient non-compliance with anti-TB regimen

5%

(1/20)

M1

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PREFERRED RESPONSE 1
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