Correspondence

Eosinophiluria and Acute Interstitial Nephritis

N Engl J Med 2008; 358:1760-1761April 17, 2008

Article

To the Editor:

Over the past two decades, testing for eosinophiluria has gained widespread acceptance as a means of screening for acute interstitial nephritis. The frequent use of this test may be explained, in part, by the subtle clinical presentation of this condition (fever, rash, arthralgia, and renal failure), which mimics other entities, such as pyelonephritis and renal manifestation of various systemic diseases. Renal biopsy, although used infrequently to diagnose acute interstitial nephritis, continues to be the gold standard.

The data on urinary eosinophil testing are inconsistent. A report in the Journal in 1986 by Nolan et al.1 states that detection of eosinophils with Hansel's stain “appears to be a sensitive marker for drug-induced acute interstitial nephritis.” Similar studies by Corwin et al.2,3 support this conclusion. All reports note a broad spectrum of diseases associated with eosinophiluria and urge caution in the interpretation of positive findings. Furthermore, a 1987 letter to the editor4 pointed out that in the report by Nolan et al., acute interstitial nephritis was not established on a histologic basis for the majority of patients. Seven years later, a study of 152 patients with pyuria and 51 patients with suspected acute interstitial nephritis5 showed that the sensitivity of eosinophiluria was 40% for the detection of acute interstitial nephritis and the positive predictive value was no greater than 38%.

Since then, little has been published on the matter, yet the clinical practice of screening urine for eosinophils to detect acute interstitial nephritis appears to have flourished. Data from our institution (unpublished) showed that 62 of 534 quantitative urinary eosinophil tests performed in 2006 showed eosinophiluria. Acute interstitial nephritis was diagnosed in only 13 patients during the same year (with no biopsy confirmation in any of the patients): in 2 patients, eosinophils accounted for more than 2% of white cells in the urine; in 6 patients, the urine was negative for eosinophils; and in 5 patients, a urinary eosinophil test was not performed. The sensitivity and positive predictive value in our institution are 25% and 3%, respectively. Interestingly, most of the tests (98%) were ordered by physicians who were not nephrologists.

In this era of evidence-based medical practice, the widespread use of a screening test with such poor sensitivity and low positive predictive value seems unjustified. In addition, the literature is inconclusive, failing to provide solid evidence that eosinophiluria is indicative of acute interstitial nephritis. At best, testing urine for eosinophils to detect acute interstitial nephritis represents a simple clinical misconception of utility and effectiveness; at worst, it represents a hazard to patients through false positive diagnosis, leading to unnecessary treatment, or false negative diagnosis, resulting in delayed renal biopsy and treatment.

Andrew Fletcher, M.D.
University of Florida, Gainesville, FL 32610
fletca@pathology.ufl.edu

5 References

1. 1

   Nolan CR III, Anger MS, Kelleher SP. Eosinophiluria -- a new method of detection and definition of the clinical spectrum. N Engl J Med 1986;315:1516-1519
   Full Text | Web of Science | Medline

2. 2

   Corwin HL, Korbet SM, Schwartz MM. Clinical correlates of eosinophiluria. Arch Intern Med 1985;145:1097-1099
   CrossRef | Web of Science | Medline

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   Corwin HL, Bray RA, Haber MH. The detection and interpretation of urinary eosinophils. Arch Pathol Lab Med 1989;113:1256-1258
   Web of Science | Medline

4. 4

   Landais P, Goldfarb B, Kleinknecht D. Eosinophiluria and drug-induced acute interstitial nephritis. N Engl J Med 1987;316:1664-1664
   Web of Science | Medline

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   Ruffing KA, Hoppes P, Blend D, Cugino A, Jarjoura D, Whittier FC. Eosinophils in urine revisited. Clin Nephrol 1994;41:163-166
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Dongmei Chen, Chunlei Luo, Zheng Tang, Yan Zhou, Huiping Chen, Caihong Zeng, Zhihong Liu. (2012) Delayed Renal Function Recovery From Drug-Induced Acute Interstitial Nephritis. The American Journal of the Medical Sciences 343:1, 36-39
   CrossRef

2. 2

   Grad, Yonatan H., Seifter, Julian L., Levy, Bruce D., Loscalzo, Joseph, . (2010) Bitter Pills. New England Journal of Medicine 363:19, 1847-1851
   Full Text

3. 3

   A. I. Joaquim, G. E. F. Mendes, P. F. F. Ribeiro, M. A. F. Baptista, E. A. Burdmann. (2010) Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study. Nephrology Dialysis Transplantation 25:10, 3277-3282
   CrossRef