背景:我们试图确定尼日利亚艾滋病毒感染者(PLWH)中镰状细胞性状(SCT)和载脂蛋白1(APOL1)风险变异的患病率,并确定SCT和APOL1高危状态是否与估计的肾小球滤过率(eGFR)和/或流行的慢性肾脏疾病(CKD)相关。
方法:在三次横断面访视期间获得基线人口统计学和临床数据。CKD定义为eGFR<60mL/min/1.73m2。我们收集尿液标本以确定尿白蛋白-肌酸比率和血样进行镰状细胞基因分型,APOL1测试,和肌酐/胱抑素C评估。SCT之间的关联,APOL1基因型,和eGFR/CKD分期/CKD使用线性/序数逻辑/逻辑回归模型进行调查,分别。
结果:在2443名参与者中,599(24.5%)有SCT,2291(93.8%)具有低风险APOL1基因型(0或1个风险变异),而152(6.2%)具有高风险基因型(2个等位基因拷贝)。总的来说,108名参与者(4.4%)被诊断为CKD。在调整后的分析中,SCT与较低的eGFR相关(校正平均差[aMD]=-2.33,95%CI-4.25,-0.42),但不是更坏的CKD阶段,或增加发展CKD的几率。APOL1高风险基因型的参与者更有可能具有较低的eGFR(aMD=-5.45,95%CI-8.87,-2.03),发展CKD(调整后比值比[aOR]=1.97,95%CI:1.03,3.75),与低风险基因型相比,处于更差的CKD阶段(aOR=1.60,95%CI:1.12,2.29)。没有证据表明SCT和APOL1基因型对eGFR或CKD风险的相互作用。
结论:我们的发现强调了遗传因素在PLWHCKD发病机制中的多方面相互作用。
BACKGROUND: We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 (APOL1) risk variants in people living with HIV (PLWH) in Nigeria, and to establish if SCT and APOL1 high-risk status correlate with estimated glomerular filtration rate (eGFR) and/or prevalent chronic kidney disease (CKD).
METHODS: Baseline demographic and clinical data were obtained during three cross-sectional visits. CKD was defined as having an eGFR<60 mL/min/1.73 m2. We collected urine specimens to determine urine albumin-creatine ratio and blood samples for sickle cell genotyping, APOL1 testing, and for creatinine/cystatin C assessment. The associations between SCT, APOL1 genotype, and eGFR/CKD stages/CKD were investigated using linear/ordinal logistic/logistic regression models, respectively.
RESULTS: Of 2443 participants, 599 (24.5%) had SCT, and 2291 (93.8%) had a low-risk APOL1 genotype (0 or 1 risk variant), while 152 (6.2%) had high-risk genotype (2 allele copies). In total, 108 participants (4.4%) were diagnosed with CKD. In adjusted analyses, SCT was associated with lower eGFR (adjusted mean difference [aMD]= -2.33, 95% CI -4.25, -0.42), but not with worse CKD stages, or increased odds of developing CKD. Participants with the APOL1 high risk genotype were more likely to have lower eGFR (aMD= -5.45, 95% CI -8.87, -2.03), to develop CKD (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.03, 3.75), and to be in worse CKD stages (aOR = 1.60, 95% CI: 1.12, 2.29) than those with the low-risk genotype. There was no evidence of interaction between SCT and APOL1 genotype on eGFR or risk of CKD.
CONCLUSIONS: Our findings highlight the multifaceted interplay of genetic factors in the pathogenesis of CKD in PLWH.