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, drugs, and toxins that damage the kidneys.
• People may have painful urination, pain in the lower back or side, fever, and a rash.
• Laboratory tests of blood and urine are used to detect kidney damage.
• Stopping exposure to harmful drugs and toxins and treating underlying disorders improve kidney function.

Tubulointerstitial nephritis may be acute or chronic, and it often results in kidney failure. It may be caused by various diseases, drugs, toxins, or radiation that damages the kidneys. Damage to the tubules results in changes in the concentrations of electrolytes in the blood or in problems with the kidney's ability to concentrate urine. There are two parts of the kidney tubules, the proximal and the distal. When the proximal tubule is damaged, the normal reabsorption into the blood of sodium, potassium, bicarbonate, uric acid, and phosphate may be altered, resulting in low levels in the blood of these substances. Injuries to the distal tubule are usually associated with a loss of urine-concentrating ability and an increase in daily urine volume (polyuria).

Secondary Causes of Tubulointerstitial Nephritis
Diseases Pyelonephritis Sarcoidosis Sickle cell disease Sjögren's syndrome Systemic lupus erythematosus (lupus) Drugs LithiumSome Trade Names LITHOBID Nonsteroidal anti-inflammatory drugs (NSAIDs) Chemotherapy drugs Anti-rejection drugs for transplant recipients (such as cyclosporineSome Trade Names NEORAL SANDIMMUNE and tacrolimusSome Trade Names PROGRAF ) Toxins Aristolochic acid Cadmium Lead

Causes

The most common cause of acute tubulointerstitial nephritis is an allergic reaction to a drug. Antibiotics such as penicillin and the sulfonamides, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs)—including aspirinSome Trade Names
BAYER
—may trigger an allergic reaction. The interval between the exposure to the allergen that caused the reaction and the development of acute tubulointerstitial nephritis varies from 5 days to 5 weeks.

Drugs can also cause tubulointerstitial nephritis through nonallergic mechanisms. For example, NSAIDs can damage the tissues gradually, 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.

Symptoms and Diagnosis

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

When tubulointerstitial nephritis develops suddenly, the amount of urine produced may be normal or less than normal. Some people develop the symptoms of pyelonephritis: fever, painful urination, pus in the urine, and pain in the lower back or side (flank). If the cause is an allergic reaction, symptoms may include fever and a rash.

When tubulointerstitial nephritis develops gradually, 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.

Laboratory 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, hypokalemia, hypouricemia, or hypophosphatemia. 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 pus, but often the abnormalities are striking. The urine may show large numbers of white blood cells, including eosinophils. Eosinophils rarely appear in the urine, but when they do, a person usually has acute tubulointerstitial nephritis caused by an allergic reaction. Also, the number of eosinophils in the blood may be increased.

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 x-rays or ultrasound scanning.

Prognosis and Treatment

Kidney function usually improves when an offending drug is discontinued or treatment of the underlying disease is effective, although some kidney scarring is common. Treatment with a corticosteroid may speed the recovery of kidney function when the disorder is caused by 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.

When the inflammation occurs gradually, kidney damage may develop at different rates in different portions of the kidney. The person may develop abnormalities characteristic of damage to different portions of the kidney at different times. However, kidney damage usually progresses to involve most or all of the kidney and becomes irreversible. Irreversible kidney damage, whatever the cause, results in the need for dialysis or kidney transplantation.

Last full review/revision March 2007 by Seyed-Ali Sadjadi, MD