METHODS: A retrospective analysis of 72 HIV-infected individuals receiving
indinavir was performed to identify the frequency and risk factors for
indinavir-associated nephropathy and urinary complications. Individuals treated with
nucleoside analogues alone served as controls.
RESULTS: Mean serum
creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum
creatinine levels > or =1.4 mg/dl. Increased serum
creatinine levels were found more frequently in women (p < 0.01) and were associated with
pyuria and microhematuria (p < 0.01). Frank
renal colic and/or
nephrolithiasis (seven patients) and urinary pH were not associated with serum
creatinine levels > or =1.4 mg/dl. The mean duration of
indinavir treatment, until sterile
pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum
creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings,
pyuria preceded the first rise in serum
creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with
pyuria,
indinavir was replaced for various reasons and
pyuria disappeared in nine. In these patients mean serum
creatinine levels decreased from 1.43 mg/dl at withdrawal of
indinavir to 1.04 mg/dl three months later (p < 0.01).
CONCLUSION:
Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition,
indinavir-associated tubulointerstitial disease does no in patients taking
indinavir may help to identify patients being at risk for nephrotoxicity.