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Human Immunodeficiency Virus...
PEDIATRICS Vol. 110 No. 2 August 2002, pp. e19-e19

ELECTRONIC ARTICLE

Persistent Sterile Leukocyturia Is Associated With Impaired Renal Function in Human Immunodeficiency Virus Type 1-Infected Children Treated With Indinavir

Annemarie M. C. van Rossum, MD, PhD*, Jeanne P. Dieleman, PhD{ddagger}, Pieter L. A. Fraaij, MD*, Karlien Cransberg, MD*, Nico G. Hartwig, MD, PhD*, David M. Burger, PharmD, PhD§, Inge C. Gyssens, MD, PhD{ddagger},|| and Ronald de Groot, MD, PhD*

* Department of Pediatrics, Sophia Children’s Hospital/Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands
{ddagger} Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands
§ Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, the Netherlands
|| Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands

Background. Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children.

Design. A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir.

Methods. Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir.

Results. The cumulative incidence of persistent sterile leukocyturia (≥75 cells/µL in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg/L*h or a peak serum level of indinavir >12 mg/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months.

Conclusions. Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir-associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg/L*h, and a Cmax >12 mg/L.

Key Words: human immunodeficiency virus • children • indinavir • nephrotoxicity

Abbreviations: HIV, human immunodeficiency virus • AUC, area under plasma-concentration curve • IQR, interquartile range

Received for publication Nov 2, 2001; Accepted Apr 8, 2002.




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