 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
15 July 1997 | Volume 127 Issue 2 | Pages 119-125
Background: Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir.
Objective: To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir.
Patients: Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health.
Measurements: Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms.
Results: Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging.
Conclusions: Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic.
Author and Article Information
From the National Institute of Diabetes and Digestive and Kidney Diseases. Warren Grant Magnuson Clinical Center, and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
ARTICLE
Crystalluria and Urinary Tract Abnormalities Associated with Indinavir
Note in Proof: Since our study of indinavir-associated urinary tract abnormalities ended in December 1996, 8 additional patients from the group of 240 described here developed urinary tract symptoms and crystalluria while receiving indinavir: Two of these 8 patients had nephrolithiasis, 5 had back or flank pain, and 1 had dysuria. Three other patients who began receiving indinavir also developed symptoms: One had nephrolithiasis, 1 had back or flank pain, and 1 had dysuria.
Acknowledgments: The authors thank the physicians and nurses of the National Institute of Allergy and Infectious Disease/Critical Care Medicine Department HIV Research Clinic and the National Institute of Allergy and Infectious Disease HIV Primary Care Clinic for their care of the patients described in this report. They also thank Mr. Daniel Hogan of Leica, Inc., for assistance with polarized microscopy and Ms. Lisa Miller and Ms. Shuying Liu for logistical support.
Grant Support: Merck & Co. provided the indinavir used in the in vitro studies.
Requests for Reprints: Jeffrey B. Kopp, MD, Building 10, Room 3N116, National Institutes of Health, Bethesda, MD 20892.
Current Author Addresses: Drs. Kopp, Miller, Mican, Feuerstein, Pannell, and Falloon and Ms. Vaughan and Ms. Baker: Building 10, National Institutes of Health, Bethesda, MD 20892.
This article has been cited by other articles:
|
|
 |
|
  M. A. Boyd, U. Siangphoe, K. Ruxrungtham, P. Reiss, A. Mahanontharit, J. M. A. Lange, P. Phanuphak, D. A. Cooper, and D. M. Burger The use of pharmacokinetically guided indinavir dose reductions in the management of indinavir-associated renal toxicity J. Antimicrob. Chemother., June 1, 2006; 57(6): 1161 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Berns and N. Kasbekar Highly Active Antiretroviral Therapy and the Kidney: An Update on Antiretroviral Medications for Nephrologists Clin. J. Am. Soc. Nephrol., January 1, 2006; 1(1): 117 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Kimmel, L. Barisoni, and J. B. Kopp Pathogenesis and Treatment of HIV-Associated Renal Diseases: Lessons from Clinical and Animal Studies, Molecular Pathologic Correlations, and Genetic Investigations Ann Intern Med, August 5, 2003; 139(3): 214 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dybul, M. Daucher, M. A. Jensen, C. W. Hallahan, T.-W. Chun, M. Belson, B. Hidalgo, D. C. Nickle, C. Yoder, J. A. Metcalf, et al. Genetic Characterization of Rebounding Human Immunodeficiency Virus Type 1 in Plasma during Multiple Interruptions of Highly Active Antiretroviral Therapy J. Virol., March 1, 2003; 77(5): 3229 - 3237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. C. van Rossum, J. P. Dieleman, P. L. A. Fraaij, K. Cransberg, N. G. Hartwig, D. M. Burger, I. C. Gyssens, and R. de Groot Persistent Sterile Leukocyturia Is Associated With Impaired Renal Function in Human Immunodeficiency Virus Type 1-Infected Children Treated With Indinavir Pediatrics, August 1, 2002; 110(2): e19 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Dieleman, M. C. J. M. Sturkenboom, M. Jambroes, I. C. Gyssens, G.-J. Weverling, J. H. ten Veen, G. Schrey, P. Reiss, B. H. Ch. Stricker, and for the ATHENA Study Group Risk Factors for Urological Symptoms in a Cohort of Users of the HIV Protease Inhibitor Indinavir Sulfate: The ATHENA Cohort Arch Intern Med, July 8, 2002; 162(13): 1493 - 1501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Edwards, A. Bansal, S. Sabbaj, J. Bakari, M. J. Mulligan, and P. A. Goepfert Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma J. Virol., March 1, 2002; 76(5): 2298 - 2305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Herman, N. J. Ives, M. Nelson, B. G. Gazzard, and P. J. Easterbrook Incidence and risk factors for the development of indinavir-associated renal complications J. Antimicrob. Chemother., September 1, 2001; 48(3): 355 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Mason Indinavir sulphate therapy associated with crystalluria and nephrolithiasis The Journal of the Royal Society for the Promotion of Health, March 1, 2001; 121(1): 7 - 8. [PDF]
|
|
|
|
 |
|
 T. J. Kanmaz and N. J. Lee Significant Toxicities Associated with Antiretroviral Therapy Journal of Pharmacy Practice, December 1, 2000; 13(6): 457 - 474. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Hanabusa, H. Tagami, and H. Hataya Renal Atrophy Associated with Long-Term Treatment with Indinavir N. Engl. J. Med., February 4, 1999; 340(5): 392 - 393. [Full Text]
|
|
|
|
 |
|
 A. Hsu, G. R. Granneman, G. Cao, L. Carothers, A. Japour, T. El-Shourbagy, S. Dennis, J. Berg, K. Erdman, J. M. Leonard, et al. Pharmacokinetic Interaction between Ritonavir and Indinavir in Healthy Volunteers Antimicrob. Agents Chemother., November 1, 1998; 42(11): 2784 - 2791. [Abstract] [Full Text]
|
|
|
|
|
|
C. Flexner HIV-Protease Inhibitors N. Engl. J. Med., April 30, 1998; 338(18): 1281 - 1293. [Full Text] [PDF]
|
|
|
|
|
|
K. C. Yeh, P. J. Deutsch, H. Haddix, M. Hesney, V. Hoagland, W. D. Ju, S. J. Justice, B. Osborne, A. T. Sterrett, J. A. Stone, et al. Single-Dose Pharmacokinetics of Indinavir and the Effect of Food Antimicrob. Agents Chemother., February 1, 1998; 42(2): 332 - 338. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Dybul, T.-W. Chun, C. Yoder, B. Hidalgo, M. Belson, K. Hertogs, B. Larder, R. L. Dewar, C. H. Fox, C. W. Hallahan, et al. Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters PNAS, December 18, 2001; 98(26): 15161 - 15166. [Abstract] [Full Text] [PDF]
|
|
Article
