Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands.
Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen , The Netherlands.
Am J Physiol Renal Physiol. 2019 Mar 1;316(3):F606-F614. doi: 10.1152/ajprenal.00425.2018. Epub 2019 Jan 9.
In physiological conditions, circulating iron can be filtered by the glomerulus and is almost completely reabsorbed by the tubular epithelium to prevent urinary iron wasting. Increased urinary iron concentrations have been associated with renal injury. However, it is not clear whether increased urinary iron concentrations in patients are the result of increased glomerular iron filtration and/or insufficient tubular iron reabsorption and if these processes contribute to renal injury. We measured plasma and urine iron parameters and urinary tubular injury markers in healthy human subjects ( n = 20), patients with systemic iron overload ( n = 20), and patients with renal tubular dysfunction ( n = 18). Urinary iron excretion parameters were increased in both patients with systemic iron overload and tubular dysfunction, whereas plasma iron parameters were only increased in patients with systemic iron overload. In patients with systemic iron overload, increased urinary iron levels were associated with elevated circulating iron, as indicated by transferrin saturation (TSAT), and increased body iron, as suggested by plasma ferritin concentrations. In patients with tubular dysfunction, enhanced urinary iron and transferrin excretion were associated with distal tubular injury as indicated by increased urinary glutathione S-transferase pi 1-1 (GSTP1-1) excretion. In systemic iron overload, elevated urinary iron and transferrin levels were associated with increased injury to proximal tubules, indicated by increased urinary kidney injury marker 1 (KIM-1) excretion. Our explorative study demonstrates that both glomerular filtration of elevated plasma iron levels and insufficient tubular iron reabsorption could increase urinary iron excretion and cause renal injury.
在生理条件下，循环铁可被肾小球滤过，几乎被肾小管上皮细胞完全重吸收，以防止尿中铁的浪费。尿铁浓度增加与肾损伤有关。然而，尚不清楚患者尿铁浓度增加是由于肾小球铁滤过增加和/或肾小管铁重吸收不足引起的，以及这些过程是否导致肾损伤。我们在健康受试者（n=20）、全身铁过载患者（n=20）和肾小管功能障碍患者（n=18）中测量了血浆和尿铁参数以及尿管状损伤标志物。全身铁过载和肾小管功能障碍患者的尿铁排泄参数均增加，而血浆铁参数仅在全身铁过载患者中增加。在全身铁过载患者中，增加的尿铁水平与循环铁升高有关，如转铁蛋白饱和度（TSAT）所示，并且与铁蛋白浓度升高有关，提示体内铁增加。在肾小管功能障碍患者中，尿谷胱甘肽 S-转移酶 pi 1-1（GSTP1-1）排泄增加表明远端肾小管损伤与增强的尿铁和转铁蛋白排泄相关。在全身铁过载中，尿铁和转铁蛋白水平升高与近端肾小管损伤相关，如尿肾损伤标志物 1（KIM-1）排泄增加所示。我们的探索性研究表明，升高的血浆铁水平的肾小球滤过和不足的肾小管铁重吸收都可能增加尿铁排泄并导致肾损伤。
