Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
Environ Int. 2023 Jul;177:107997. doi: 10.1016/j.envint.2023.107997. Epub 2023 May 30.
Ultrafine particles, including black carbon (BC), can reach the systemic circulation and therefore may distribute to distant organs upon inhalation. The kidneys may be particularly vulnerable to the adverse effects of BC exposure due to their filtration function.
We hypothesized that BC particles reach the kidneys via the systemic circulation, where the particles may reside in structural components of kidney tissue and impair kidney function.
In kidney biopsies from 25 transplant patients, we visualized BC particles using white light generation under femtosecond-pulsed illumination. The presence of urinary kidney injury molecule-1 (KIM-1) and cystatin c (CysC) were evaluated with ELISA. We assessed the association between internal and external exposure matrices and urinary biomarkers using Pearson correlation and linear regression models.
BC particles could be identified in all biopsy samples with a geometric mean (5th, 95th percentile) of 1.80 × 10 (3.65 × 10, 7.50 × 10) particles/mm kidney tissue, predominantly observed in the interstitium (100 %) and tubules (80 %), followed by the blood vessels and capillaries (40 %), and the glomerulus (24 %). Independent from covariates and potential confounders, we found that each 10 % higher tissue BC load resulted in 8.24 % (p = 0.03) higher urinary KIM-1. In addition, residential proximity to a major road was inversely associated with urinary CysC (+10 % distance: -4.68 %; p = 0.01) and KIM-1 (+10 % distance: -3.99 %; p < 0.01). Other urinary biomarkers, e.g., the estimated glomerular filtration rate or creatinine clearance showed no significant associations.
Our findings that BC particles accumulate near different structural components of the kidney represent a potential mechanism explaining the detrimental effects of particle air pollution exposure on kidney function. Furthermore, urinary KIM-1 and CysC show potential as air pollution-induced kidney injury biomarkers for taking a first step in addressing the adverse effects BC might exert on kidney function.
超细颗粒,包括黑碳(BC),可以到达体循环,因此吸入后可能会分布到远处的器官。由于肾脏的过滤功能,它们可能特别容易受到 BC 暴露的不利影响。
我们假设 BC 颗粒通过体循环到达肾脏,颗粒可能存在于肾脏组织的结构成分中,并损害肾脏功能。
在 25 名移植患者的肾活检组织中,我们使用飞秒脉冲照射下的白光产生来观察 BC 颗粒。使用 ELISA 评估尿肾损伤分子 1(KIM-1)和胱抑素 C(CysC)的存在。我们使用 Pearson 相关和线性回归模型评估内部和外部暴露矩阵与尿生物标志物之间的关联。
所有活检样本中均能识别出 BC 颗粒,肾组织中颗粒的几何平均值(第 5 个、第 95 个百分位数)为 1.80×10(3.65×10,7.50×10)颗粒/mm 组织,主要分布于间质(100%)和小管(80%),其次是血管和毛细血管(40%)和肾小球(24%)。独立于协变量和潜在混杂因素,我们发现组织 BC 负荷每增加 10%,尿 KIM-1 增加 8.24%(p=0.03)。此外,与主要道路的居住距离较近与尿 CysC 呈负相关(距离增加 10%:-4.68%;p=0.01)和 KIM-1(距离增加 10%:-3.99%;p<0.01)。其他尿生物标志物,如估计肾小球滤过率或肌酐清除率与 BC 无显著相关性。
我们发现 BC 颗粒在肾脏的不同结构成分附近积聚,这代表了一种潜在的机制,可以解释颗粒空气污染暴露对肾脏功能的有害影响。此外,尿 KIM-1 和 CysC 可能成为空气污染诱导的肾脏损伤生物标志物,为解决 BC 对肾脏功能可能产生的不利影响迈出了第一步。