无症状患者尿中阿扎那韦和达芦那韦浓度高和出现结晶尿。

High levels of atazanavir and darunavir in urine and crystalluria in asymptomatic patients.

机构信息

Infectious Diseases Department, St Louis Hospital, APHP and Sorbonne Paris Cité, University Paris Diderot, Paris, France.

出版信息

J Antimicrob Chemother. 2013 Aug;68(8):1850-6. doi: 10.1093/jac/dkt125. Epub 2013 Apr 18.

DOI:10.1093/jac/dkt125

PMID:23599359

Abstract

OBJECTIVES

Atazanavir has been associated with kidney stones and renal failure. We measured urine and plasma concentrations of recent protease inhibitors (PIs) and searched for PI crystals in the urine of asymptomatic patients.

METHODS

A cross-sectional analysis of HIV-infected patients taking ritonavir-boosted atazanavir 300 mg/day (ATV300/r), unboosted atazanavir 400 mg/day (ATV400), ritonavir-boosted darunavir at either 800 mg/day (DRV800/r) or 1200 mg/day (DRV1200/r) or ritonavir-boosted lopinavir 800 mg/day was performed. Plasma and urine were collected and PI levels measured using HPLC. Crystals were detected and identified in urine using polarized microscopy.

RESULTS

PI levels were measured in 266 patients, 142 of whom were assessed for urinary crystals. Their mean age was 46 years. The mean duration of HIV infection was 10.5 years and the mean duration of the current PI-containing regimen was 22.5 months. The mean CD4 cell count was 494 cells/mm(3); 74% showed controlled HIV replication. Median urinary PI levels were 22.3, 14.3, 26.9 and 29.7 mg/L for ATV300/r, ATV400, DRV800/r and DRV1200/r, respectively, significantly higher than plasma levels, which were all <5 mg/L (P < 0.001). In contrast, median urinary lopinavir concentrrations did not significantly differ from plasma concentrations (4.2 and 6.4 mg/L, respectively; P = 0.7) and were significantly lower than those of other PIs (P < 0.001). Atazanavir crystals were found in 7/78 patients receiving ATV300/r (8.9%; 95% CI = 2.6%-15.2%) and darunavir crystals were found in 4/51 patients receiving darunavir (7.8%; 95% CI = 0.4%-15.2%). Longer exposure to atazanavir was the only risk factor associated with the presence of atazanavir crystalluria (P = 0.04).

CONCLUSIONS

Unlike lopinavir, atazanavir and darunavir reached high concentrations in urine. Urinary crystals were found in a few patients receiving ritonavir-boosted atazanavir or darunavir and may favour nephrolithiasis.

摘要

目的

阿扎那韦与肾结石和肾衰竭有关。我们测定了无症状患者尿液和血浆中的近期蛋白酶抑制剂（PI）浓度，并在尿液中寻找 PI 晶体。

方法

对接受利托那韦增效阿扎那韦 300 mg/天（ATV300/r）、未增效阿扎那韦 400 mg/天（ATV400）、利托那韦增效达芦那韦 800 mg/天（DRV800/r）或 1200 mg/天（DRV1200/r）或利托那韦增效洛匹那韦 800 mg/天的 HIV 感染患者进行了横断面分析。收集血浆和尿液，并用 HPLC 测定 PI 水平。用偏光显微镜检测尿液中的晶体并鉴定其类型。

结果

共检测了 266 例患者的 PI 水平，其中 142 例评估了尿液晶体。患者的平均年龄为 46 岁。HIV 感染的平均时间为 10.5 年，当前含 PI 方案的平均时间为 22.5 个月。平均 CD4 细胞计数为 494 个/立方毫米；74%患者 HIV 复制得到了控制。ATV300/r、ATV400、DRV800/r 和 DRV1200/r 的尿液 PI 中位数分别为 22.3、14.3、26.9 和 29.7 mg/L，明显高于血浆水平（均＜5 mg/L，P＜0.001）。相反，洛匹那韦的尿液浓度与血浆浓度无显著差异（分别为 4.2 和 6.4 mg/L，P=0.7），且明显低于其他 PI（P＜0.001）。在接受利托那韦增效阿扎那韦或达芦那韦的患者中，7/78 例（8.9%；95%CI=2.6%-15.2%）发现阿扎那韦晶体，4/51 例（7.8%；95%CI=0.4%-15.2%）发现达芦那韦晶体。较长时间接受阿扎那韦是与阿扎那韦结晶尿相关的唯一危险因素（P=0.04）。