Reid Andrew, Stöhr Wolfgang, Walker A Sarah, Williams Ian G, Kityo Cissy, Hughes Peter, Kambugu Andrew, Gilks Charles F, Mugyenyi Peter, Munderi Paula, Hakim James, Gibb Diana M
University of Zimbabwe, Harare, Zimbabwe.
Clin Infect Dis. 2008 Apr 15;46(8):1271-81. doi: 10.1086/533468.
We sought to investigate renal function in previously untreated symptomatic human immunodeficiency virus (HIV)-infected adults with CD4(+) cell counts of <200 cells/mm(3) who were undergoing antiretroviral therapy (ART) in Africa.
The study was an observational analysis within a randomized trial of ART management strategies that included 3316 participants with baseline serum creatinine levels of < or =360 micromol/L. Creatinine levels were measured before ART initiation, at weeks 4 and 12 of therapy, and every 12 weeks thereafter. We calculated estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula. We analyzed the incidence of severely decreased eGFR (<30 mL/min/1.73 m(2)) and changes in eGFR to 96 weeks, considering demographic data, type of ART, and baseline biochemical and hematological characteristics as predictors, using random-effects models.
Sixty-five percent of the participants were women. Median values at baseline were as follows: age, 37 years; weight, 57 kg; CD4(+) cell count, 86 cells/mm(3); and eGFR, 89 mL/min/1.73 m(2). Of the participants, 1492 (45%) had mild (> or =60 but <90 mL/min/1.73 m(2)) and 237 (7%) had moderate (> or =30 but <60 mL/min/1.73 m(2)) impairments in eGFR. First-line ART regimens included zidovudine-lamivudine plus tenofovir disoproxil fumarate (for 74% of patients), nevirapine (16%), and abacavir (9%) (mostly nonrandomized allocation). After ART initiation, the median eGFR was 89-91 mL/min/1.73 m(2) for the period from week 4 through week 96. Fifty-two participants (1.6%) developed severe reductions in eGFR by week 96; there was no statistically significant difference between these patients and others with respect to first-line ART regimen received (P = .94). Lower baseline eGFR or hemoglobin level, lower body mass index, younger age, higher baseline CD4(+) cell count, and female sex were associated with greater increases in eGFR over baseline, with small but statistically significant differences between regimens (P < .001 for all).
Despite screening, mild-to-moderate baseline renal impairment was relatively common, but these participants had greatest increases in eGFR after starting ART. Severe eGFR impairment was infrequent regardless of ART regimen and was generally related to intercurrent disease. Differences between ART regimens with respect to changes in eGFR through 96 weeks were of marginal clinical relevance, but investigating longer-term nephrotoxicity remains important.
我们试图在非洲对未曾接受过治疗且有症状的、CD4(+)细胞计数<200个细胞/mm³的成人艾滋病病毒（HIV）感染者进行抗逆转录病毒治疗（ART）时，研究其肾功能。
该研究是一项ART管理策略随机试验中的观察性分析，纳入了3316名基线血清肌酐水平≤360微摩尔/升的参与者。在开始ART前、治疗第4周和第12周以及此后每12周测量肌酐水平。我们使用Cockcroft-Gault公式计算估计肾小球滤过率（eGFR）。我们将人口统计学数据、ART类型以及基线生化和血液学特征作为预测因素，采用随机效应模型分析eGFR严重降低（<30毫升/分钟/1.73平方米）的发生率以及至96周时eGFR的变化。
65%的参与者为女性。基线时的中位数如下：年龄37岁；体重57千克；CD4(+)细胞计数86个细胞/mm³；eGFR 89毫升/分钟/1.73平方米。参与者中，1492人（45%）eGFR有轻度（≥60但<90毫升/分钟/1.73平方米）损害，237人（7%）有中度（≥30但<60毫升/分钟/1.73平方米）损害。一线ART方案包括齐多夫定-拉米夫定加替诺福韦酯（74%的患者）、奈韦拉平（16%）和阿巴卡韦（9%）（大多为非随机分配）。开始ART后，第4周至第96周期间eGFR的中位数为89 - 91毫升/分钟/1.73平方米。到第96周时，52名参与者（1.6%）eGFR严重降低；这些患者与接受其他一线ART方案的患者相比，差异无统计学意义（P = 0.94）。较低的基线eGFR或血红蛋白水平、较低的体重指数、较年轻的年龄、较高的基线CD4(+)细胞计数以及女性性别与eGFR相对于基线的更大升高相关，不同方案之间存在虽小但有统计学意义的差异（所有P < 0.001）。
尽管进行了筛查，但轻度至中度基线肾功能损害相对常见，但这些参与者开始ART后eGFR升高幅度最大。无论ART方案如何，严重eGFR损害都不常见，且通常与并发疾病有关。至96周时不同ART方案在eGFR变化方面的差异临床相关性不大，但研究长期肾毒性仍然很重要。
