1. Description of the problem

What every clinician needs to know

Interstitial nephritis is usually caused by medications and is responsible for approximately 10% of cases of acute kidney injury (AKI). The most common medications are antibiotics (cephalosporins and quinolones), nonsteroidal anti-inflammatory agents, H2 antagonists and bisphosphonates. Less common causes include infections and systemic diseases. The incidence of interstitial nephritis is probably underestimated since kidney biopsies are rarely performed for AKI and the clinical features are nonspecific.

Clinical features

Interstitial nephritis develops within days to a few weeks of drug exposure. There is no relationship between its development and cumulative dose. Patients present with symptoms of edema, hypertension, diminished urine output and AKI. The classic manifestations of allergic phenomena such as skin rash, arthralgias, fever, eosinophilia and eosinophiluria are present in only a minority of patients. Flank pain is occasionally a prominent feature on presentation. Clues to the presence of interstitial nephritis are signs of renal tubular dysfunction, including Fanconi syndrome and renal tubular acidosis.

Key management points

Treatment first should be directed at stopping any offending medications, treating any infections, and providing disease specific treatment for systemic disease. In patients with worsening renal function despite such therapy, a short course of corticosteroids is probably worthwhile. The typical regimen is prednisone, 1 mg/Kg/day for 1-3 weeks depending on the clinical course.

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2. Emergency Management

Interstitial nephritis is usually not an emergent medical condition but develops over time. Most emergent management would relate to manifestations of severe renal failure, including life-threatening hyperkalemia, metabolic acidosis, volume overload and electrolyte disorders. Dialysis is rarely necessary for patients with interstitial nephritis.

3. Diagnosis

Diagnostic criteria and tests

The clinical features of interstitial nephritis are non-specific, therefore diagnosis is often one of exclusion and requires a high index of suspicion. The classical manifestations of allergic phenomema are present in only a minority of patients. Blood chemistries, urinalysis, and urine eosinophils should be ordered. Blood chemistries may reveal the presence of a renal tubular acidosis and hyperkalemia, as well as determine the degree of renal failure.

Urinalysis may reveal microscopic hematuria, white blood cell casts and sterile pyuria. The presence of urinary eosinophils is of limited value, as the positive predictive value of finding urinary eosinophils in the diagnosis of interstitial nephritis is only 40%.

Establishing the diagnosis

Clues to the presence of interstitial nephritis:

  • Non-oliguric AKI

  • Microscopic or macroscopic hematuria

  • Sterile pyuria

  • White blood cell casts

  • Renal tubular acidosis

  • Fanconi syndrome

  • Eosinophilia and eosinophiluria

  • Fever

  • Skin rash

  • Arthralgias

Other possible diagnoses
  • Cholesterol emboli syndrome

  • Systemic vasculitis

Confirmatory tests

Renal biopsy is the only confirmatory test and is rarely indicated. It is usually performed when renal failure doesn’t improve and prolonged dialysis is anticipated.

4. Specific Treatment

Non-specific therapy includes stopping any offending agents, treating any infectious process and providing disease specific treatments when indicated.

The use of corticosteroids remains controversial. Positive observational data with corticosteroids are limited to small case series. These studies suggest an association with a more rapid recovery from renal failure with their use.

Drugs and dosages

Prednisone 1 mg/kg/day for 1-3 weeks depending on clinical response.

Refractory cases

Refractory cases require a renal biopsy to confirm the diagnosis. When corticosteroids have failed, small case series with other immunosuppressant agents such as mycophenolate mofetil have been reported, but such therapies should be considered strictly experimental.

5. Disease monitoring, follow-up and disposition

Given the various causes of interstitial nephritis, there is no uniform clinical course. In classic antibiotic induced interstitial nephritis, the prognosis is excellent and renal recovery is greater than 90%. The prognosis may be worse in other forms of interstitial nephritis.

Incorrect diagnosis

When renal function does not improve and a patient has failed a trial of steroids, another diagnosis should be considered and renal biopsy performed. Subsequent treatment will depend on the biopsy findings and ranges from supporting care to the use of various immunosuppressive agents.


If renal recovery is complete, routine medical followup is recommended. If not, then followup with nephrology is recommended.


Interstitial nephritis is an immunological reaction to a variety of medications, infectious agents or systemic diseases confined mainly to the interstitial compartment of the renal parenchymal. Therefore, many of the clinical manifestations of interstitial nephritis are the result of dysfunction of the renal tubules.

The interstitial infiltrate is predominantly mononuclear with T- and B-lymphocytes, macrophages and natural killer cells. The infiltrate results in interstitial edema, disruption of tubular basement membrane and destruction of the interstitial architecture.


Hospital acquired AKI develops in 5-7% of patients and may be as high as 35% in critically ill patients. It is estimated that 10% of these cases are due to interstitial nephritis. However, this is probably an underestimate since renal biopsies are rarely performed and the findings of interstitial nephritis are non-specific and often absent.

It can be very difficult to establish a direct link between a particular drug and interstitial nephritis because patients receive a variety of potentially nephrotoxic medications, making it uncertain whether the etiology is interstitial nephritis or drug-induced acute tubular necrosis. Also, co-morbid conditions are usually present that could cause renal dysfunction.


Given the various causes of interstitial nephritis, there is no uniform course. In classically described methacillin induced interstitial nephritis, the overall prognosis is excellent, with renal recovery expected in more than 90% of patients. In patients with other drug-induced interstitial nephritis, the prognosis may not be as good: chronic kidney disease has been reported to be as high as 40%. The prognosis may be especially poor for interstitial nephritis associated with non-steroidal anti-inflammatory agents and acute bacterial infection.

Special considerations for nursing and allied health professionals.


What's the evidence?

Michel, DM, Kelly, CJ. “Acute interstitial nephritis”. J Am Soc Nephrol. vol. 9. 1998. pp. 506-15. (Excellent overview of the topic of interstitial nephritis.)

Linton, AL, Clark, WF, Driedger, AA, Turnbull, DI, Lindsay, RM. “Acute interstitial nephritis due to drugs: Review of the literature with a report of nine cases”. Ann Intern Med. vol. 93. 1980. pp. 735-41. (Review of classic agents associated with drug-induced interstitial nephritis.)

Clarkson, MR, Giblin, L, O’Connell, FP. “Acute interstitial nephritis: Clinical features and response to corticosteroid therapy”. Nephrol Dial Transplant. vol. 19. 2004. pp. 2778-83. (Case series of patients with interstitial nephritis and response to steroid administration.)

Galpin, JE, Shinaberger, JH, Stanley, TM. “Acute interstitial nephritis due to methacillin”. Am J Med. vol. 65. 1978. pp. 756-65. (Classic paper that reviews the association of interstitial nephritis and methacillin.)

Preddie, DC, Markowitz, GS, Radhakrishnan, J. “Mycophenolate mofetil for the treatment of interstitial nephritis”. Clin J Am Soc Nephrol. vol. 1. 2006. pp. 718-22. (Small case series describing the response of interstitial nephritis to mycophenolate mofetil.)

Ruffing, KA, Hoppes, P, Blend, D, Cugino, A, Jarjoura, D. “Eosinophils in urine revisited”. Clin Nephrol. vol. 41. 1994. pp. 163-6. (Excellent review of the utility of urinary eosinophils in accurately diagnosing interstitial nephritis.)

Rossert, J. “Drug-induced acute interstitial nephritis”. Kidney Int. vol. 60. 2001. pp. 804-17. (A good overview of drug-induced interstitial nephritis.)

Gonzales, C, Gutierrez, C, Galeano, C. “Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis”. Kidney Int. vol. 73. 2008. pp. 940-6. (A case series of patients with drug-induced interstitial nephritis and the response to steroids.)