Acute interstitial nephritis

• Incidence
• Predisposing Factors
• Microscopic Features
• Natural History
• Clinical History
• Clinical Examination
• General Investigation
• Specific Investigations
• Prognosis
• Treatment Overview
• References
• Treatments Used in This Disease

Incidence

Acute interstitial nephritis contributes 10-15% of all kidney diseases both in the US and around the world.²

Predisposing Factors

Acute interstitial nephritis (AIN) has no racial predilections. Generally, sex does not have any influence on having the disease, except for analgesic nephropathy, which is 5-6 times more common in women. This is attributed to women taking more analgesics than men. The role of women’s physiology in pathogenesis of analgesic nephropathy is unknown.
AIN affects all ages, however, it must be remembered that renal toxicity is dependent on the cumulative effects of toxic substances. This means that the more the kidney is damaged due to toxic substances, the higher the risk of the kidney suffering from subsequent damage. Also, advanced age is a risk factor for AIN because kidney function generally declines with age.

Microscopic Features

The disease primarily affects the interstitium and sometimes the tubules. Hence, it is characterised histologically by interstitial oedema accompanied by leukocytic infiltration. Sometimes, focal tubular necrosis may be found. The leukocytes found are mostly eosinophils and neutrophils (seen below).

Natural History

AIN has many causes with the most common being drug-induced. One review of 128 patients with AIN identified the following causes:¹

• Drugs: 71% (with one third caused by antibiotics);
• Infection: 15%;
• Idiopathic: 8%;
• Tubulointerstitial nephritis and uveitis (TINU) syndrome: 5%;
• Sarcoidosis: 1%.

The principle pathogenesis in drug-induced acute interstitial nephritis is hypersensitivity reaction to drugs, such as penicillin, NSAIDs, and sulfa-containing drugs.

Clinical History

AIN usually presents with non-specific symptoms, such as:

• Nausea and vomiting;
• Generalised weakness;
• Lethargy.

However, it must be remembered that AIN can be symptomless. It is important to establish if any new drugs have been started, particularly pain-killers and antibiotics. Also, the use of complementary or alternative medicines needs to be established. The patient should also be asked if they have had any recent infections, including viral illnesses.

Clinical Examination

Clinical examination might not reveal any relevant findings as kidney disease does not usually present with any specific signs. However, patients with drug-induced AIN might have signs of an allergic-type reaction. This includes:

• Rash: occurs in 15% of the patients.
• Fever: occurs in 27% of the patients.

General Investigation

The patient usually needs a complete workup.
A routine set of general blood investigations will include:

• Full blood count: may show an increased white cell count;
• Liver function tests;
• Renal function tests: may show increased creatinine;
• Electrolytes: may show potassium abnormalities if in acute renal failure

Urinalysis will be done to examine the urine. Positive urinalysis findings include:

• Presence of white blood cells in the urine;
• Presence of red blood cells in the urine;
• Presence of protein in the urine.

However, it must be remembered that occasionally the patient’s urinalysis may come back normal – described as ‘bland urinalysis’. A relatively normal urinalysis does not exclude the diagnosis of AIN.

Specific Investigations

In order to diagnose the disease, some or all of the following tests may be done:

• Blood eosinophil count: eosinophils are a type of white blood cell involved in the allergic response; therefore, they may be elevated in AIN. However, this is generally not the case in NSAID-induced AIN.
• Urine microscopy: this involves taking a sample of the urine and examining it under the microscope. Typically, a collection of cells may be found in the urine, known as granular and epithelial cell casts. If blood cells are found, they are called red cell or white cell cast. By doing this test, other causes of acute renal failure can be ruled out.
• Renal biopsy: this involves taking a sample of the kidney and examining it under the microscope. Although this is the definitive diagnostic test for AIN, it is an invasive procedure with potentially serious complications. Hence, this is only reserved in patients in which a definitive diagnosis is needed.

Another imaging study that can be done, albeit infrequently, is a gallium scan, which is a nuclear medicine imaging technique.

Prognosis

The overall prognosis for AIN is excellent. Most patients’ renal function recovers upon cessation of the offending agent. The improvement occurs within 6-8 weeks. However, recovery may be incomplete leading to persistent elevation in plasma creatinine concentration.

Treatment Overview

The most important part of treatment is cessation of the offending agent. This includes a complete review of the patient’s current medications and stopping any drugs that may potentially be causing AIN. If the patient does not show any symptoms and signs of improvement (in terms of clinical symptoms as well as blood results), corticosteroids can be administered to suppress inflammation. Evidence suggests that immunosuppressants (eg cyclophosphamide or mycophenolate mofetil) may be beneficial in AIN that doesn’t respond to the cessation of the offending agent.

References

1. Baker RJ, Pusey CD. The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant. 2004;19(1):8-11. [Abstract| Full text]
2. Nephritis, interstitial [online]. eMedicine; 2005. [cited 15 October 2005]. Available from: URL link
3. Clinical manifestations and diagnosis of acute interstitial nephritis [online]. Up to Date; 2005 [cited 15 October 2005]. Available from: URL link
4. Treatment of acute interstitial nephritis [online]. Up to Date; 2005 [cited 15 October 2005]. Available from: URL link

Treatments Used in This Disease:

• Kidney Transplant;
• Corticosteroids;
• Immunosuppressants.