Acute Interstitial Nephritis (AIN) is a disorder affecting the kidneys characterized by the rapid onset of inflammation within the kidney’s structure. This inflammation leads to a sudden decline in kidney function, known as acute kidney injury (AKI). AIN is recognized as a significant cause of AKI, accounting for 10% to 20% of all hospitalized cases. It is an immune-mediated injury where the body’s defense system mistakenly attacks the kidney tissue.
Defining Acute Interstitial Nephritis
Acute Interstitial Nephritis refers to inflammation specifically located in the renal interstitium, the space surrounding the kidney’s tiny filtering units and tubules. The interstitium is the connective tissue that provides structural support and houses the blood vessels and immune cells surrounding these tubules.
In AIN, this interstitial space becomes filled with inflammatory cells, such as lymphocytes, macrophages, and eosinophils, leading to swelling and damage. This cellular infiltration and resulting edema impair the ability of the renal tubules to reabsorb water and regulate electrolytes. Since the renal tubules and the interstitium are both involved, the condition is sometimes described more accurately as acute tubulointerstitial nephritis.
Primary Triggers and Causes
AIN is predominantly caused by an immune response, often a hypersensitivity reaction, to an external trigger, with medications being the most frequent culprit. More than 100 different drugs have been identified as potential triggers. The drug acts as a hapten, binding to tubular cells and causing the immune system to launch an attack against the kidney tissue.
Common classes of medications known to cause this reaction include certain antibiotics, such as penicillin and cephalosporins, and nonsteroidal anti-inflammatory drugs (NSAIDs). Proton pump inhibitors (PPIs), widely used to treat stomach acid issues, are also increasingly recognized as a cause, particularly in older adults. The reaction to a medication can occur anywhere from a few days to several months after starting the drug.
Beyond drug exposure, AIN can also be triggered by systemic infections, such as those caused by certain bacteria or viruses. Autoimmune disorders, including systemic lupus erythematosus or Sjögren syndrome, also represent a less common category of causes. In these cases, the inflammation is part of a broader body-wide immune malfunction rather than a reaction to a specific drug.
Clinical Presentation and Detection
The symptoms of AIN often present as acute kidney injury. A patient may experience a sudden change in urination, which can manifest as either a decrease or, in some cases, an increase in urine output. Other general symptoms include nausea, vomiting, fatigue, and swelling in the body due to fluid retention.
The classic triad of symptoms—fever, rash, and a high level of eosinophils (a type of white blood cell) in the blood—is often taught but occurs in only 5% to 10% of cases. Therefore, a high degree of suspicion is necessary, especially if a patient has recently started a new medication. Laboratory testing typically shows elevated levels of serum creatinine and blood urea nitrogen (BUN), which indicate reduced kidney function.
While blood and urine tests can suggest the diagnosis, a kidney biopsy remains the most definitive method for confirmation. The tissue sample is examined under a microscope for the characteristic presence of inflammatory cells and edema within the interstitium. The biopsy is used to confirm AIN, especially if kidney function does not improve after discontinuing the suspected drug.
Therapeutic Approaches
The immediate therapeutic step for AIN is the prompt identification and cessation of the causative agent, whether it is a drug or an underlying infection. Discontinuing the offending medication can often lead to a rapid and complete recovery of kidney function, especially if the condition is caught early. Supportive care is also provided to manage the consequences of acute kidney injury, such as managing fluid balance, controlling blood pressure, and regulating electrolytes.
Corticosteroids, such as prednisone, are frequently used to suppress the immune-mediated inflammation. While controlled clinical trials are limited, many clinicians use these agents, believing they may speed up the recovery of kidney function and reduce the chances of long-term damage. Treatment with steroids is usually considered if kidney function does not quickly improve after the causative agent is removed.
The overall prognosis is often favorable, with many patients regaining most or all of their original kidney function. However, some patients may be left with residual kidney impairment. In severe cases, temporary dialysis may be necessary to support the body during the acute phase of kidney failure. Long-term follow-up is necessary to monitor for any lasting effects and to ensure that potentially harmful medications are avoided in the future.