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Indinavir and Interstitial Nephritis
- Jeffrey B. Kopp, MD;
- Kirk D. Miller, MD; and
- Judith Falloon, MD
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IN RESPONSE:
Sarcletti and colleagues inquire about the frequency of persistent renal dysfunction in patients with indinavir-associated flank pain and crystalluria, particularly those with renal parenchymal defects on computed tomography. In our series of 240 patients receiving indinavir, 13 patients (5%) developed such symptoms. Computed tomography was done during the acute episode in 6 patients and revealed parenchymal defects in 4 patients. Of these 4 patients, 2 have discontinued indinavir therapy permanently because of symptoms, 1 has continued indinavir therapy at a reduced dosage (1800 mg/d), and 1 has continued indinavir therapy at the full dosage (2400 mg/d). Of all 13 patients with flank pain-crystalluria, 4 discontinued therapy after 2 to 8 months of therapy and 8 are still receiving full-dosage indinavir therapy (mean treatment duration, 14 months [range, 10 to 18 months]). No patient has manifested persistent renal dysfunction (defined as a serum creatinine level > 0.2 mg/dL above the baseline value).
We agree with Sarcletti and colleagues that the cumulative frequency of flank pain-crystalluria seems to increase with longer duration of indinavir therapy. It is less clear that the cumulative frequency of renal parenchymal abnormalities on computed tomography increases with longer duration of therapy; all four patients with these findings presented within 18 weeks of the initiation of therapy.
Sarcletti and colleagues also raise the issue of female susceptibility to indinavir-associated renal injury. Of the 240 patients who received indinavir in our series, 14 (6%) were women. Of the 13 patients who developed flank pain-crystalluria, 2 (15%) were women. We believe that the data are too limited to allow us to draw conclusions at this time.
We believe that indinavir therapy is associated with a continuum of crystal-related renal syndromes, including frank nephrolithiasis, flank pain (with or without renal parenchymal defects on computed tomography), dysuria, and asymptomatic crystalluria. We have recently identified several indinavir-treated patients who have developed pyuria in whom the pyuria resolved upon discontinuation of indinavir therapy. Renal function has remained normal in these patients, and the source of the urinary leukocytes has not been identified. The relation of these syndromes to the cases of interstitial nephritis reported by Tashima and coworkers [1] and Sarcletti and colleagues remain to be determined. We share the concern that exposure of the renal tubular epithelium to indinavir crystals may produce interstitial inflammation and persistent renal dysfunction. Nevertheless, we have not seen evidence for this in our patients; this suggests that such renal injury is relatively uncommon. We think that patients receiving indinavir should have renal function monitored and urinalysis performed, and we agree that the long-term impact of indinavir crystalluria on the kidney is not known.
Jeffrey B. Kopp, MD
Kirk D. Miller, MD
Judith Falloon, MD
National Institutes of Health; Bethesda, MD 20892
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
