Hospital Medicine

Acute Interstitial Nephritis

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Medication-Induced Kidney Failure/Allergic Interstitial Nephritis

I. What every physician needs to know.

Allergic interstitial nephritis (AIN) is an immune mediated kidney injury most commonly induced by drugs such as nonsteroidal anti-inflammatory drugs (NSAIDS) and antibiotics. Less common causes of AIN include infections such as Legionella, cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Mycobacterium tuberculosis, Streptococcus and many autoimmune systemic diseases including sarcoidosis, systemic lupus erythematosus (SLE) and Sjogrens. Pathology of AIN demonstrates an inflammatory interstitial infiltrate which may progress to fibrosis and irreversible renal failure.

II. Diagnostic Confirmation: Are you sure your patient has Allergic Interstitial Nephritis?

Allergic interstitial nephritis should be suspected in patients presenting with acute kidney injury and recent exposure to a drug known to cause AIN. Urinalysis can show red blood cells, white blood cells and white cell casts. The complete blood count (CBC) reveals eosinophilia in up to 1/3 of patients but eosinophiluria has less predictive value. A definitive diagnosis is made by renal biopsy.

A. History Part I: Pattern Recognition:

Systemic symptoms of allergic interstitial nephritis may include fever, nausea and malaise. The classic triad of fever, rash and eosinophilia is seen in less than 10% of cases. Onset of symptoms average 10 days after initiation of the offending drug but may begin sooner with repeated exposure and occasionally may not present for months. Drugs that most commonly cause AIN are:

  • NSAIDS

  • Penicillins, Cephalosporins

  • Sulfonamides

  • Diuretics, both loop and thiazide types

  • Rifampin

  • Macrolides

  • Ciprofloxacin

  • Cimetidine

  • Allopurinol

  • Proton pump inhibitors

B. History Part 2: Prevalence:

Elderly patients are more likely to have drug induced AIN especially with penicillins, as opposed to AIN from autoimmune or systemic diseases.

C. History Part 3: Competing diagnoses that can mimic Allergic Interstitial Nephritis.

The diagnostic evaluation for AIN should include ruling out other common causes of acute kidney injury and obstruction. The urinalysis may often times be helpful, but can be bland as well. The triad of acute kidney injury, rash and eosinophilia may also be seen with atheroembolic renal disease and should be suspected in any patient who recently underwent vascular surgery or cardiac catheterization.

D. Physical Examination Findings.

Approximately 15% of patients with allergic interstitial nephritis present with a maculopapular rash. Many patients are asymptomatic.

E. What diagnostic tests should be performed?

AIN may present with a maculopapular rash.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Often the diagnosis of AIN can presumptively be made based on clinical presentation and urine studies. In the setting of renal failure with recent drug exposure, urinalysis with red and white blood cells, white cell casts and mild proteinuria suggests AIN. It is important to note that a normal urinalysis does not exclude AIN. Eosinophilia and eosinophiluria is less common with NSAID induced AIN. The gold standard for diagnosis of AIN is renal biopsy, which shows an interstitial infiltrate composed mostly of T-lymphocytes and monocytes. Biopsy is generally not performed unless the diagnosis is unclear, the patient does not improve following cessation of the offending drug, or if the patient is being considered for treatment with glucocorticoids.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Renal ultrasound may be ordered as part of the workup for acute renal failure, however, there are no pathognomonic signs for AIN on ultrasound.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Urine eosinophils have lower predictive power for AIN than white blood cells and white cell casts.

III. Default Management.

The mainstay of treatment for allergic interstitial nephritis is to stop the offending medication. Several observational and retrospective studies have suggested that steroids may be beneficial in preventing long-term renal dysfunction and it is usually reserved for patients who do not recover renal function following drug cessation. One retrospective study found greater benefit if prednisone was initiated within 7 days of presentation, however, the optimal dose and duration remains unclear.

A. Immediate management.

Dialysis is occasionally necessary to treat volume overload, electrolyte abnormalities, or other complications of acute renal failure (see acute renal failure).

B. Physical Examination Tips to Guide Management.

Monitor urine output and watch for any signs of worsening acute renal failure that would necessitate initiation of dialysis.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Creatinine should be followed daily until it has stabilized. If kidney function does not improve consider renal biopsy to confirm diagnosis.

D. Long-term management.

Up to 50% of patients may not return to baseline renal function. A small percentage may require long-term dialysis.

E. Common Pitfalls and Side-Effects of Management.

For AIN which does not improve with cessation of the offending medication, prednisone 1 milligram/kilogram (mg/kg) for 3 weeks followed by a slow taper over one month may be initiated. There is not a studied optimal treatment duration.

A. Renal Insufficiency.

Per above.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

The optimal approach to AIN in patients who are on chronic glucocorticoids is unknown. There is very limited data suggesting that mycophenolate mofetil can potentially be helpful in this class of patients.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

A. Sign-out considerations While Hospitalized.

N/A

B. Anticipated Length of Stay.

N/A

C. When is the Patient Ready for Discharge.

The patient may be discharged when creatinine has stabilized and any electrolyte abnormalities have resolved.

D. Arranging for Clinic Follow-up.

Patient should follow up with their primary care provider within one week for a repeat basic metabolic panel. If renal insufficiency persists, they should be followed by the renal subspecialist.

1. When should clinic follow up be arranged and with whom.

N/A

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

A repeat basic metabolic panel should be ordered on the day of the follow-up visit.

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

Between 30 and 70% of patients do not completely return to baseline renal function. Less than 10% will require long-term dialysis.

A. Core Indicator Standards and Documentation.

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Avoid re-administration of drug class which led to AIN.

**The original authors for this chapter was Dr. David Mintzer. The chapter was revised by Dr. Jacklyn Lee.

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