Imagine starting a new, common medication, like an antibiotic or a pain reliever, only to find yourself feeling unusually tired and unwell a week or two later, with blood tests revealing a sudden decline in your kidney function. This unexpected and frightening scenario is often the presentation of Acute Interstitial Nephritis (AIN). AIN is a serious kidney condition characterized by inflammation within the kidney tissue itself. It is crucial to understand that in most cases, AIN is not a primary kidney disease, but rather a rare and unpredictable allergic-type reaction to a medication. It is a major cause of acute kidney injury (AKI), but with prompt recognition, withdrawal of the offending agent, and treatment to calm the inflammation, the kidneys can often make a full recovery.

Acute Interstitial Nephritis, also known as tubulointerstitial nephritis, is a condition involving inflammation of the renal interstitium and the renal tubules of the kidney. To understand this, it helps to first distinguish between the different parts of the kidney’s functional unit, the nephron.

• The glomeruli are the millions of tiny, complex balls of capillaries that act as the kidney’s main filters, removing waste products from the blood.
• The tubules are the long, sophisticated pipes that come after the filters. Their job is to reabsorb essential water and electrolytes back into the blood while concentrating the waste into urine.
• The interstitium is the delicate “scaffolding” or connective tissue that surrounds and supports all these tubules.

A helpful analogy is to think of your kidney as a massive coffee-making factory.

• The glomeruli are the millions of tiny coffee filters that separate the waste (the coffee grounds) from the good liquid.
• The interstitium and tubules are all the factory’s “back-office” spaces, the hallways, plumbing, and structural supports that lie between the filters.
• In many common kidney diseases, like glomerulonephritis, the problem is with the filters themselves becoming clogged or damaged.
• In Acute Interstitial Nephritis, the filters are perfectly fine. Instead, a severe allergic reaction causes the body’s inflammatory “SWAT team” to flood all the hallways and back-office spaces.
• This massive inflammation and swelling outside the filters compresses the plumbing and disrupts the entire factory’s operation from the inside out, causing the kidney to shut down. This is the essence of AIN.

In my experience, many patients with interstitial nephritis present with vague symptoms like fatigue or back pain, only to be diagnosed after routine blood work shows impaired kidney function.

The direct cause of AIN is the infiltration of the kidney’s interstitium with inflammatory white blood cells, such as T-cells and eosinophils. This inflammatory response leads to swelling and damage to the tubules, impairing the kidney’s ability to function.

The underlying causes that trigger this inflammatory reaction can be grouped into three main categories.

1. Allergic Reactions to Medications

This is, by far, the most common cause, accounting for over 70% of all cases of AIN. It is an idiosyncratic, allergic-type hypersensitivity reaction, meaning it is an unpredictable and rare side effect, not a predictable toxic effect of the drug. Hundreds of medications have been implicated, but the most common culprits include:

• Antibiotics: Penicillins, cephalosporins, and sulfa drugs are classic triggers.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Common over-the-counter pain relievers like ibuprofen and naproxen.
• Proton Pump Inhibitors (PPIs): A very common class of drugs used to treat acid reflux, such as omeprazole and pantoprazole.
• Certain Diuretics (“Water Pills”).

2. Infections

In some cases, the inflammation can be a direct result of the kidneys being infected with a specific organism.

• Bacterial Infections: Including Streptococcus, Legionella, and, importantly in many parts of the world, Tuberculosis (TB).
• Viral Infections: Such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and HIV.

3. Autoimmune Diseases

AIN can be a manifestation of a systemic autoimmune disease where the immune system is attacking multiple tissues in the body, including the kidneys.

• Lupus (Systemic Lupus Erythematosus)
• Sjögren’s Syndrome
• Sarcoidosis
• A specific condition called Tubulointerstitial Nephritis with Uveitis (TINU) syndrome, which primarily affects adolescents and young women.

Clinically, I’ve most commonly seen it caused by medications especially NSAIDs, antibiotics like penicillin and proton pump inhibitors.

A person develops AIN due to one of the underlying triggers listed above. It is not contagious and it is not an inherited disease. The primary risk factor is simply being exposed to a triggering medication, developing a specific infection, or having a systemic autoimmune disease. Because drug reactions are the most common cause, taking multiple medications (polypharmacy), especially in older adults, can increase the chance of exposure to a potential trigger.

In my experience, patients often develop it after starting a new medication especially if they’re taking multiple nephrotoxic drugs or have underlying kidney stress.

The symptoms of AIN can be very vague, non-specific, or even completely absent in the early stages. Often, the first sign of the condition is a rise in the serum creatinine level on a routine blood test, indicating a decline in kidney function.

The “classic triad” of symptoms often associated with drug-induced AIN is actually only seen in a small minority of patients (less than 10-15%). This triad includes:

1. Fever
2. Skin Rash
3. Eosinophilia (a high level of a specific type of white blood cell, the eosinophil, in the blood).

When symptoms do occur, they are typically those of acute kidney injury (AKI). These can include:

• Fatigue, malaise, and a general feeling of being unwell.
• Nausea and loss of appetite.
• A decrease in urine output (oliguria).
• Fluid retention, leading to swelling in the legs (edema).
• In some cases, a dull pain in the flank area over the kidneys.

Patients may report nonspecific symptoms like flank pain, fever, rash, or joint aches but I also look for signs of fluid retention or reduced urine output.

A diagnosis of AIN is typically suspected by a nephrologist (a kidney specialist) when a patient develops acute kidney injury, especially if it occurs one to two weeks after starting a new medication. The diagnostic workup is focused on confirming inflammation in the kidney and ruling out other causes of AKI.

1. Medical History: A thorough review of all of a patient’s recent medications including prescription, over-the-counter, and herbal supplements, is the most critical first step.
2. Blood Tests:
   • A blood chemistry panel will show a rising serum creatinine and blood urea nitrogen (BUN), confirming the presence of acute kidney injury.
   • A complete blood count (CBC) may show an elevated eosinophil count.
3. Urine Tests: A urinalysis is a very important part of the workup.
   • The urine may show the presence of white blood cells (pyuria) and, characteristically, white blood cell casts. White blood cell casts are clumps of white blood cells formed in the kidney tubules and are a strong indicator of inflammation within the kidney itself.
   • The urine may also be specifically tested for the presence of eosinophils.
4. Kidney Ultrasound: An ultrasound is typically performed to rule out a physical blockage (like a kidney stone or an enlarged prostate) as the cause of the kidney injury.
5. Kidney Biopsy: The gold standard and only definitive way to diagnose acute interstitial nephritis is with a kidney biopsy.
   • In this procedure, a doctor uses a long, thin needle, usually guided by ultrasound, to remove a tiny core sample of kidney tissue.
   • The tissue is sent to a pathologist who examines it under a microscope. The definitive finding is the presence of inflammatory cells infiltrating the interstitium and tubules of the kidney.

In my experience, it’s important to rule out other causes of acute kidney injury especially prerenal and postrenal causes before attributing findings to interstitial nephritis.

The treatment for AIN is focused on removing the trigger, suppressing the inflammation, and supporting the patient while the kidneys heal.

1. Withdrawal of the Offending Agent

This is the absolute first and most important step in treatment.

• If a medication is the suspected cause, it must be discontinued immediately.
• If an underlying infection is the cause, it must be treated with appropriate antibiotics.
• If it is part of a systemic autoimmune disease, treatment will be directed at that underlying condition.

In many mild cases, simply stopping the offending drug is enough to allow the kidney inflammation to subside and function to recover over several weeks.

2. Corticosteroids

For more severe cases of drug-induced AIN, especially if kidney function does not begin to improve after stopping the trigger drug, a course of corticosteroids is the mainstay of treatment.

• A high dose of prednisone is typically given, either orally or intravenously, to aggressively suppress the allergic-type inflammation within the kidneys.
• It is believed that starting steroid therapy early improves the chances of a faster and more complete recovery of kidney function. The steroid course is typically tapered off over several weeks.

3. Supportive Care

If the acute kidney injury is severe, hospitalization is required for supportive care. This involves:

• Careful management of fluid balance and electrolytes.
• Medications to control blood pressure.
• Dialysis: In severe cases where the kidneys shut down completely, the patient will require temporary dialysis. Dialysis is a life-saving procedure that takes over the job of the kidneys, cleaning the blood of waste products and removing excess fluid. This is often a temporary bridge, used for days to weeks, waiting for the kidneys to heal and recover their function.

The prognosis for AIN is generally good if the condition is recognized early and the trigger is removed. Many people recover complete or near-complete kidney function, although some may be left with a degree of chronic kidney disease.

Clinically, I’ve found that supportive care and early intervention prevent progression to chronic kidney disease especially in drug-induced cases.

Acute Interstitial Nephritis is a serious cause of acute kidney injury that results from inflammation in the kidney’s supportive tissues. It is most often an unpredictable allergic reaction to a common medication. While its symptoms can be vague, the key to diagnosis is recognizing a decline in kidney function after a new exposure. The cornerstone of management is prompt identification and withdrawal of the offending drug. With early diagnosis and, when necessary, a course of corticosteroids to quell the inflammation, the kidneys have a remarkable ability to heal. Most patients can expect a full recovery. Clinically, I’ve seen that careful medication review and prompt discontinuation of culprits are often all that’s needed to restore normal kidney function.

1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2014). Interstitial Nephritis. Retrieved from https://www.niddk.nih.gov/health-information/kidney-disease/interstitial-nephritis
2. The Merck Manual Professional Version. (2023). Tubulointerstitial Nephritis. Retrieved from https://www.merckmanuals.com/professional/genitourinary-disorders/tubulointerstitial-diseases/tubulointerstitial-nephritis
3. The National Kidney Foundation. (n.d.). Acute Kidney Injury (AKI). Retrieved from https://www.kidney.org/atoz/content/AcuteKidneyInjury