What Causes Acute Interstitial Nephritis?
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Acute Interstitial Nephritis - Causes, Symptoms, and Treatment

Published on Dec 21, 2022 and last reviewed on May 12, 2023   -  4 min read


Acute interstitial nephritis presents renal failure and is the common cause of acute kidney disease. To know more, read the article below.


Acute interstitial nephritis is one of the significant causes of kidney disease. It manifests as renal failure and other extrarenal complications depending on the cause of acute interstitial nephritis. William Thomas's councilman first described it in 1898. Acute interstitial nephritis has been associated with various factors such as infections, drugs, and systemic disorders.

What Is the Cause of Acute Renal Failure?

Acute interstitial nephritis has been associated with infections, drugs, and systemic disorders. Drugs are the common cause of acute interstitial nephritis in all age groups. Antibiotics such as Cephalosporins, Penicillins, Ciprofloxacin, and nonsteroidal anti-inflammatory drugs frequently cause acute renal failure. Rifampicin, proton pump inhibitors, 5-aminosalicylates, Acyclovir, and Allopurinol, are other drugs that cause acute interstitial nephritis. Acute interstitial nephritis is the most common renal condition in acute kidney injury, which is associated with immune checkpoint inhibitors, for example, Pembrolizumab. Studies have shown that any drug can precipitate acute interstitial nephritis, and the list of offending medicines has been increasing. Infections that cause acute interstitial nephritis involve:

The systemic disorder that causes acute interstitial nephritis includes Sjogren's syndrome, sarcoidosis, IgG-4-related systemic disorders, and systemic lupus erythematosus (SLE). In rare cases, idiopathic acute interstitial nephritis has been reported in association with TINU syndrome (tubulointerstitial nephritis and uveitis syndrome) and anti-tubular basement membrane disease. TINU syndrome manifests as an abnormal renal function from interstitial nephritis and acute onset of granulomatous uveitis, which presents with redness, photophobia, and pain. Renal involvement is followed by eye manifestations or can occur simultaneously. TINU syndrome is common in younger adults (below 20 years) and children. It shows a female predilection with no ethnic specificity. TINU is reported in one to two percent of Ophthalmology cases. TINU may be caused due to genetic susceptibility and infectious and iatrogenic factors. TNU is suspected by three criteria involving:

  • Decreased creatinine clearance or abnormal creatinine.

  • Defective urine analysis (microscopic hematuria, low-grade proteinuria, sterile pyuria, eosinophiluria, white blood cell casts, and elevated b2 microglobulin).

  • Systemic illness lasting more than two weeks (weight loss, fever, fatigue, increased erythrocyte sedimentation rate, abnormal liver enzyme, and anemia).

Anti-tubular basement membrane disease manifests as chronic kidney disease or acute kidney injury in all age groups. Polyuria (excess urination) and polydipsia (feeling extremely thirsty) are common symptoms. In addition, sub-nephrotic range proteinuria and microscopic hematuria (blood in the urine) can be detected.

Is Acute Interstitial Nephritis Common?

A kidney biopsy achieves an affirmative diagnosis. However, not all cases require kidney biopsies as there may be an improvement in the individual's renal function after the offending agent is stopped or the nephritis is treated empirically. According to studies, acute interstitial nephritis is present in 1 % to 10 % of all kidney biopsies suspected of glomerulonephritis. The biopsies performed for acute kidney injury had a higher incidence of acute interstitial nephritis. Drug-induced acute interstitial nephritis comprises two-thirds of all cases of acute interstitial nephritis. Idiopathic causes account for 5 % to 10 %, systemic disorders at 10 % to 15 %, and infections at 10 % to 15 % for the majority of the causes of acute interstitial nephritis. Older individuals are prone to drug-induced acute interstitial nephritis compared to younger individuals.

What Is the Pathophysiology of Acute Interstitial Nephritis?

The immune response mediates the drug-induced acute interstitial nephritis. The drugs bind to cytoplasmic or extracellular components of tubular cells, creating a host immune response. Some individuals show a type 1 hypersensitivity reaction with elevated IgE (immunoglobulin E) serum levels. Other cases present a T-cell-mediated type-IV hypersensitivity reaction with eosinophilia, rash, and detection of positive skin tests. The exact pathophysiology is unclear. Microbial agents may deposit in the interstitium and mimic the antigen in the tubular basement membrane, creating an immune response.

What Are the Signs and Symptoms of Acute Interstitial Nephritis?

Acute interstitial nephritis usually manifests as non-oliguric acute kidney injury. There are cases where oliguria (low urine output of less than 400 milliliters a day) may be present. It may take several or months for the kidney injury to occur, for example, NSAIDs (nonsteroidal anti-inflammatory drugs) in individuals who are naive to the drug. A second exposure to the drug may manifest symptoms in a few days. Individuals may present with nonspecific symptoms such as vomiting, nausea, flank pain, and malaise. Studies have shown that 40 % of acute interstitial nephritis may lead to dialysis requiring renal failure. Other symptoms are related to the etiology, such as systemic lupus erythematosus or sarcoidosis. Drug-induced acute interstitial nephritis may show signs of rash, eosinophilia, and low-grade fever. These symptoms may infrequently appear in the individual. The extrarenal manifestations are specific to infections. When the cause is a systemic disorder, the symptoms are associated with that particular disease.

How Is Acute Interstitial Nephritis Diagnosed?

The physician may pay attention to the latent period if it is drug-induced acute interstitial nephritis. Symptoms such as rash, low-grade fever, and eosinophilia are present in only 10 % of cases of acute interstitial nephritis. Common urinary detection includes subnephrotic range proteinuria and pyuria. Sediment examination may reveal white blood cells. Nephrotic range proteinuria is seen with NSAIDs. Urine eosinophils are a diagnostic marker but lack specificity and sensitivity. A kidney biopsy is a definitive diagnosis.

What Is the Treatment for Acute Interstitial Nephritis?

Drug-induced acute interstitial nephritis may be resolved by discontinuing the offending drug. A definitive diagnosis is obtained by renal biopsy. The delay in corticosteroid therapy and the extent of interstitial fibrosis may impact residual renal damage. In severe cases, dialysis may be the choice of treatment. Early initiation of steroids can be helpful. Corticosteroids reduce T-cell-mediated inflammation and diminish the development of fibrosis and renal damage. The suggested regimen includes intravenous Methylprednisolone 500 mg for three days, followed by oral Prednisolone one mg (milligrams) per kg (kilograms) for two weeks.

What Are the Complications of Acute Interstitial Nephritis?

The complications include:

What Is the Prognosis for Acute Interstitial Nephritis?

Drug-induced acute interstitial nephritis shows 40 to 50 percent residual renal damage. NSAIDs associated with acute interstitial nephritis have a poor prognosis. The factors affecting prognosis are delayed starting of corticosteroid therapy, duration of acute kidney injury, interstitial fibrosis, and tubular atrophy.


Acute interstitial nephritis is the common cause of acute kidney disease. It includes causes, and drug-induced acute interstitial nephritis is a common cause. Investigations may consist of renal biopsy. Individuals should be educated about the harmful effects of the offending drugs.

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Last reviewed at:
12 May 2023  -  4 min read




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