Understanding Leukocytes in Urine
Leukocytes, or white blood cells (WBCs), are the body's primary defense against infection and inflammation [1.5.4]. When they appear in the urine in higher-than-normal numbers, it's a condition called pyuria. A normal finding is typically between 0 to 5 WBCs per high-power field (WBC/HPF) in a microscopic examination of urine sediment [1.5.1, 1.5.3]. A count of 10 or more WBCs per cubic millimeter is often defined as pyuria [1.5.2].
While the most common cause of pyuria is a urinary tract infection (UTI), the presence of leukocytes doesn't automatically confirm an infection [1.8.2]. When leukocytes are found but standard urine cultures show no bacterial growth, the condition is known as sterile pyuria [1.6.4, 1.8.3]. This signals inflammation from a non-bacterial source, and medications are a significant and often overlooked cause [1.3.3, 1.3.6].
The Link Between Medications and Leukocyturia
Medications are a primary cause of sterile pyuria, often by inducing a condition called acute interstitial nephritis (AIN) [1.3.6]. AIN is an immune-mediated kidney injury where inflammatory cells infiltrate the kidney's interstitium (the space between the kidney tubules) [1.4.1]. Over two-thirds of AIN cases are caused by adverse drug reactions [1.4.3]. This inflammation leads to leukocytes, particularly a type called eosinophils, spilling into the urine [1.2.2, 1.4.1].
Drugs can act as haptens, binding to proteins in the kidney tubules and triggering an allergic, T-cell-driven immune response [1.7.1]. This reaction is not dose-dependent and can occur from days to months after initial exposure to the drug [1.4.1, 1.4.4].
Common Medications That Cause Leukocytes in Urine
A wide range of medications can cause drug-induced AIN and subsequent pyuria. Some of the most frequently implicated classes include:
- Antibiotics: This is the most common category. Beta-lactam antibiotics like penicillins and cephalosporins, as well as fluoroquinolones, sulfonamides, and rifampin, are well-known culprits [1.4.3, 1.4.5].
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Widely used drugs like ibuprofen and aspirin can lead to AIN, often after long-term use (typically 6-18 months) [1.2.4, 1.4.4]. Unlike antibiotic-induced AIN, classic allergic symptoms like fever and rash are less common with NSAIDs [1.4.4].
- Proton Pump Inhibitors (PPIs): Medications used to reduce stomach acid, such as omeprazole and other '-prazole' drugs, are a significant cause of AIN [1.3.6, 1.4.3]. The onset can be delayed, sometimes appearing weeks after starting the medication [1.4.4].
- Diuretics: Certain 'water pills' used to treat high blood pressure and fluid retention are also associated with sterile pyuria [1.2.5, 1.3.3].
- Other Medications: A variety of other drugs have been linked to leukocyturia, including certain anticonvulsants (phenytoin, carbamazepine), antivirals (acyclovir), and allopurinol [1.4.3, 1.2.1].
Comparison: Medication-Induced Pyuria vs. UTI
Distinguishing between pyuria caused by medication and that from a bacterial UTI is crucial for proper treatment. Relying solely on the presence of leukocytes can be misleading [1.8.4].
| Feature | Medication-Induced Pyuria (Sterile Pyuria) | Urinary Tract Infection (UTI) |
|---|---|---|
| Urine Culture | Negative for significant bacteria [1.8.3] | Positive for bacteria (typically >10^5 CFU/mL) [1.5.5] |
| Key Cause | Inflammatory reaction to a drug (e.g., AIN) [1.3.6] | Bacterial invasion and growth, most commonly E. coli [1.8.2] |
| Common Symptoms | May be asymptomatic or have non-specific symptoms like fatigue. A classic (but rare) triad includes fever, rash, and joint pain [1.4.1, 1.4.4]. | Burning urination (dysuria), urinary frequency, urgency, cloudy or foul-smelling urine [1.5.4, 1.8.2]. |
| Other Lab Findings | May show eosinophils in urine, rising serum creatinine [1.4.1]. | May show positive nitrites on a dipstick test [1.8.4]. |
| Primary Treatment | Discontinuation of the offending medication [1.9.1]. Corticosteroids may be considered [1.4.6]. | A course of antibiotics [1.9.1]. |
Diagnosis and Management
Diagnosing drug-induced pyuria starts with a thorough review of the patient's medication history, both prescription and over-the-counter [1.3.2]. A urinalysis will confirm the presence of WBCs, and a urine culture will rule out a bacterial infection [1.5.4]. Blood tests to check kidney function (serum creatinine) and look for signs of allergic reaction (peripheral eosinophilia) are also important [1.4.1]. In some cases, a kidney biopsy is required for a definitive diagnosis of AIN [1.4.1, 1.7.1].
The cornerstone of management for drug-induced AIN and pyuria is to identify and withdraw the causative drug [1.4.3, 1.9.1]. In many cases, kidney function improves after the medication is stopped. If renal failure persists, a course of corticosteroids may be administered to reduce the inflammation, though this decision depends on the specific clinical situation [1.4.1, 1.4.6].
Conclusion
While a urinary tract infection is the most frequent reason for finding leukocytes in urine, it is far from the only one. A significant number of common medications, from antibiotics and NSAIDs to proton pump inhibitors, can trigger an inflammatory or allergic reaction in the kidneys, leading to drug-induced sterile pyuria. Recognizing this possibility is essential for accurate diagnosis, avoiding unnecessary antibiotic use, and initiating the correct management—which begins with stopping the offending drug. If you have concerns about your urine or medications, consulting a healthcare professional is always the right course of action.
For more in-depth information on drug-induced kidney injury, a valuable resource is the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
