Urine eosinophils for acute interstitial nephritis

Sutton¹¹ reviewed data from 10 studies and found AIN could not be reliably excluded in the absence of UEs (only 19 of 32 biopsy-confirmed AIN cases had UEs present). In addition, Ruffing et al.¹² used Hansel stain and concluded that the positive predictive value of UEs was inadequate in diagnosing AIN. Only 6 of their 15 patients with AIN had positive UEs. Urine eosinophils were also present in patients with other diagnoses (glomerulonephritis, chronic kidney disease, acute pyelonephritis, prerenal azotemia). Like many other investigators, Ruffing et al. made the AIN diagnosis on clinical grounds in the large majority of cases.

Muriithi et al.¹³ reported similarly negative results in their retrospective AKI study involving 566 Mayo Clinic patients and spanning almost 2 decades. The study included patients who underwent both Hansel-stain UE testing and kidney biopsy within a week of each other. Only 28 (30%) of 91 biopsy-proven AIN cases were positive for UEs. Using the 1% cutoff for a positive UE test yielded only 30.8% sensitivity and 68.2% specificity. Using the 5% cutoff increased specificity to 91.2%, at the expense of sensitivity (19.2%); positive predictive value improved to only 30%, and negative predictive value remained relatively unchanged, at 85.6%. In short, Muriithi et al. found that UE testing had no utility in AIN diagnosis.

In summary, initial studies, such as those by Corwin et al,^9,10 supported the conclusion that UEs are useful in AIN diagnosis but had questionable validity owing to methodologic issues, including small sample size and lack of biopsy confirmation of AIN. On the other hand, more recent studies, such as the one conducted by Muriithi et al.,¹³ had larger sample sizes and biopsy-proven diagnoses and confirmed the poor diagnostic value of UEs in AIN.

The poor sensitivity and specificity of UE tests can have important consequences. A false positive test may cause the clinician to incorrectly diagnose the patient with AIN and prompt the clinician to remove medications that may be vitally important. The clinician may also consider treating the patient with steroids empirically. A false negative test may inappropriately reassure the clinician that the patient does not have AIN and does not need cessation of the culprit drug. This may also lead the clinician to forego a necessary kidney biopsy.

WHAT YOU SHOULD DO INSTEAD

A history of recent exposure to a classic offending drug (eg, beta-lactam, proton pump inhibitor, nonsteroidal anti-inflammatory drug) in combination with the classic triad of fever, rash, and peripheral eosinophilia suggests an AIN diagnosis. However, less than 5% to 10% of patients present with this triad.^14,15 Regardless of the triad’s presence, if other causes of AKI have been excluded, stopping a potential offending agent and monitoring for improvement are recommended. If a culprit drug cannot be safely discontinued, renal biopsy may be necessary for confirmation of the diagnosis. Moreover, if kidney function continues to deteriorate, a nephrology consultation may be warranted for guidance on the risks and benefits of performing a kidney biopsy to confirm the diagnosis and/or the use of corticosteroids.

• Urine eosinophils should not be used in the diagnosis of AIN.
• The clinical diagnosis of drug-associated AIN should be based on excluding other possible likely etiologies of AKI and confirming the history of drug exposure. This is reinforced when kidney function improves upon discontinuation of offending agent.
• Kidney biopsy is the gold standard for AIN and should be performed if the clinical picture is unclear or the renal function is not improving upon discontinuation of offending agent.

Since the mid-1980s, studies have found that UEs are too insensitive and nonspecific to confirm or exclude the diagnosis of AIN in patients with AKI (Table). UEs are seen in other AKI etiologies, such as pyelonephritis, acute tubular necrosis, atheroembolic renal disease, and glomerulonephritis. Current evidence-based medicine does not support use of UEs as a biomarker for AIN. False-positive and false-negative results confuse the overall picture and result either in discontinuation of important medications and unnecessary steroid treatment or in delayed removal of a culprit medication.¹⁶

Our case’s positive UE test does not affect the posttest probability that our patient has AIN. Presence of a culprit drug and absence of clinical data suggesting an alternative diagnosis would lead most clinicians to change antibiotic therapy and observe for improvement in renal function.

Disclosure

Nothing to report.

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