Tubulointerstitial Nephritis

ByFrank O'Brien, MD, Washington University in St. Louis
Reviewed/Revised Aug 2023
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Tubulointerstitial nephritis is inflammation that affects the tubules of the kidneys and the tissues that surround them (interstitial tissue).

  • This disorder may be caused by diseases, medications, and toxins that damage the kidneys.

  • People may have excessive urination, urinate at night, or have fever and/or a rash.

  • Laboratory tests of blood and urine are done as well as usually imaging tests and sometimes a kidney biopsy.

  • Stopping exposure to the offending medications or toxins and treating underlying disorders improve kidney function.

(See also Overview of Kidney Filtering Disorders.)

Tubulointerstitial nephritis may be

  • Acute (sudden)

  • Chronic (gradual)

Tubulointerstitial nephritis often results in kidney failure (loss of most kidney function). It may be caused by various diseases, medications, toxins, or radiation that damages the kidneys. Damage to the tubules results in changes in the amounts of electrolytes (for example, sodium and potassium) in the blood or in problems with the kidney's ability to concentrate urine, resulting in urine that is too dilute. Problems concentrating urine causes an increase in daily urine volume (polyuria) and difficulty maintaining the proper balance of water and electrolytes in the blood.

Secondary Causes of Tubulointerstitial Nephritis

  1. Diseases

  2. Medications

    • Chemotherapy medications

    • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  3. Toxins

    • Aristolochic acid

    • Cadmium

    • Lead

Causes of Tubulointerstitial Nephritis

Medications can also cause tubulointerstitial nephritis through nonallergic mechanisms. For example, NSAIDs can directly damage the kidney, taking up to 18 months to cause chronic tubulointerstitial nephritis.

Infection of the kidneys (pyelonephritis) can also cause acute or chronic tubulointerstitial nephritis. Kidney failure is unlikely unless inflammation causes a blockage in the urinary tract or pyelonephritis occurs in both kidneys.

Tubulointerstitial nephritis may be caused by immunologic disorders that primarily affect the kidney such as anti-tubular basement membrane (anti-TBM) antibody–-associated interstitial nephritis.

Symptoms of Tubulointerstitial Nephritis

Some people have few or no symptoms. When symptoms develop, they are highly variable and may develop suddenly or gradually.

Acute tubulointerstitial nephritis

When tubulointerstitial nephritis develops suddenly, the amount of urine produced may be normal or less than normal. Sometimes the amount of urine produced is excessive and people urinate more frequently and waken during the night to urinate (nocturia). If the cause is pyelonephritis, symptoms may include fever, painful urination, and pain in the lower back or side (flank). If the cause is an allergic reaction, symptoms may include fever and a rash.

Chronic tubulointerstitial nephritis

When tubulointerstitial nephritis develops gradually and progressively worsens, the first symptoms to appear are those of kidney failure, such as itchiness, fatigue, decreased appetite, nausea, vomiting, and difficulty breathing. Blood pressure is normal or only slightly above normal in the early stages of the disease. The amount of urine produced may be greater than normal.

Diagnosis of Tubulointerstitial Nephritis

  • Laboratory tests

  • Sometimes imaging tests

Laboratory tests (kidney function tests) usually detect signs of kidney failure, such as an increase in the level of waste products in the blood, or other characteristic abnormalities, such as metabolic acidosis and low levels of potassium, uric acid, or phosphate. A kidney biopsy is the only conclusive means of diagnosing tubulointerstitial nephritis, although a biopsy is rarely done except when the cause cannot be found or treatment with corticosteroids is being considered.

When tubulointerstitial nephritis develops suddenly, the urine may be almost normal, with only a trace of protein or a few white blood cells, but often the abnormalities are striking. The urine may show large numbers of white blood cells, including eosinophils. Eosinophils do not normally appear in the urine, but when they do, a person may have acute tubulointerstitial nephritis caused by an allergic reaction. In such cases, blood tests may show that the number of eosinophils in the blood is increased.

A doctor may order ultrasonography, radionuclide scanning, or both. When an allergic reaction is the cause, the kidneys usually are large because of inflammation caused by the allergic reaction. This enlargement can be seen with radionuclide scanning or ultrasonography, which are imaging studies done to differentiate acute tubulointerstitial nephritis from other sudden kidney disorders.

Lab Test
Lab Test

Treatment of Tubulointerstitial Nephritis

  • Treatment of the cause

  • Corticosteroids

  • Dialysis or kidney transplantation

Acute tubulointerstitial nephritis

The first step in treating acute tubulointerstitial nephritis is to stop exposure to whatever medication or toxin is causing the kidney damage and treat the underlying disorder. Treatment with a corticosteroid may speed the recovery of kidney function when tubulointerstitial nephritis is caused by certain disorders (such as systemic lupus erythematosus or Sjögren syndrome) or an allergic reaction. If kidney function worsens and kidney failure develops, dialysis is usually needed. In some cases, the damage is irreversible, and kidney failure becomes chronic.

Chronic tubulointerstitial nephritis

Chronic tubulointerstitial nephritis is treated by stopping the causative medication or toxin, or treating the underlying disorder. Supportive care such as controlling blood pressure is often used. Medications may be used to try to slow progression of kidney disease. Irreversible severe kidney damage, whatever the cause, results in the need for dialysis or kidney transplantation.

Prognosis for Tubulointerstitial Nephritis

Kidney function usually improves when an offending medication is stopped or treatment of the underlying disorder is effective, although some kidney scarring is common. The prognosis tends to be worse when the offending medication is a nonsteroidal anti-inflammatory drug (NSAID).

When the inflammation occurs gradually, kidney damage may develop at different rates in different portions of the kidney. In some cases, kidney damage progresses to involve most or all of both kidneys and becomes irreversible.

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