title: Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir.
abstract: 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.
  
  
  METHODS
  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 (> or =75 cells/ micro L 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 x 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 x h, and a C(max) >12 mg/L.
authors.affiliation: Department of Pediatrics, Sophia Children's Hospital/Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.
authors.forename: Annemarie M C
authors.initials: AM
authors.lastname: van Rossum
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Dieleman
authors.forename: Pieter L A
authors.initials: PL
authors.lastname: Fraaij
authors.forename: Karlien
authors.initials: K
authors.lastname: Cransberg
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Inge C
authors.initials: IC
authors.lastname: Gyssens
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
mesh_terms: D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000652:urine; D007964:Leukocytosis / Q000209:etiology* / Q000652:urine*; D008297:Male; D011446:Prospective Studies; D016482:Urinalysis
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D003404:Creatinine