Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir
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 (> 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.
|Keywords||Child, Child, Preschool, Creatinine/blood, Female, HIV Infections/*drug therapy/urine, HIV Protease Inhibitors/*adverse effects/therapeutic use, HIV-1, Humans, Indinavir/*adverse effects/therapeutic use, Kidney Diseases/*chemically induced/*diagnosis/urine, Leukocytosis/*etiology/*urine, Male, Prospective Studies, Urinalysis|
Dieleman, J.P., Fraaij, P.L.A., Cransberg, K., Hartwig, N.G., Burger, D.M., Gyssens, I.C., … van Rossum, A.M.C.. (2002). Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir. Pediatrics (English Edition). Retrieved from http://hdl.handle.net/1765/9944