Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, USA.
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sci Rep. 2023 Oct 27;13(1):18406. doi: 10.1038/s41598-023-45404-9.
We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.
我们评估了线粒体 DNA 拷贝数 (mtDNA CN) 与注射吸毒者 (PWID) 队列中肾功能标志物的前瞻性关联。这是一项前瞻性队列研究,嵌套在艾滋病与静脉内经验队列 (巴尔的摩的基于社区的 PWID 队列) 中。使用实时聚合酶链反应在相隔 5 年的两个时间点测量 mtDNA CN。每年测量肾功能 (估计肾小球滤过率 [eGFR]、血清肌酐、尿蛋白)。我们使用线性混合效应模型评估肾功能轨迹 (N = 946),并使用 Cox 回归模型评估 CKD 事件的风险 (两次连续就诊时 eGFR < 60,N = 739) 和蛋白尿 (尿蛋白:肌酐比 > 200,N = 573) 按 mtDNA CN 水平 (低 [最低四分位数],与高 [其他三个四分位数]。模型调整了人口统计学和行为特征、HIV 和/或 HCV 感染以及合并症负担。低 mtDNA CN 与 CKD 事件的发生风险增加独立相关 (aHR:2.33,95%CI 1.42,3.80) 和蛋白尿 (aHR:1.42,95%CI 1.04,1.96)。mtDNA CN 低的参与者在 eGFR 下降和血清肌酐升高方面的下降幅度更大。mtDNA CN 低与肾功能下降更快和 CKD 及蛋白尿事件的发生风险增加相关。