Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Molecular and Translational Kidney Research, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nat Rev Nephrol. 2021 May;17(5):335-349. doi: 10.1038/s41581-021-00394-7. Epub 2021 Feb 5.
Kidney damage varies according to the primary insult. Different aetiologies of acute kidney injury (AKI), including kidney ischaemia, exposure to nephrotoxins, dehydration or sepsis, are associated with characteristic patterns of damage and changes in gene expression, which can provide insight into the mechanisms that lead to persistent structural and functional damage. Early morphological alterations are driven by a delicate balance between energy demand and oxygen supply, which varies considerably in different regions of the kidney. The functional heterogeneity of the various nephron segments is reflected in their use of different metabolic pathways. AKI is often linked to defects in kidney oxygen supply, and some nephron segments might not be able to shift to anaerobic metabolism under low oxygen conditions or might have remarkably low basal oxygen levels, which enhances their vulnerability to damage. Here, we discuss why specific kidney regions are at particular risk of injury and how this information might help to delineate novel routes for mitigating injury and avoiding permanent damage. We suggest that the physiological heterogeneity of the kidney should be taken into account when exploring novel renoprotective strategies, such as improvement of kidney tissue oxygenation, stimulation of hypoxia signalling pathways and modulation of cellular energy metabolism.
肾脏损伤的类型取决于原发性损伤。急性肾损伤 (AKI) 的不同病因，包括肾脏缺血、接触肾毒物、脱水或脓毒症，与特征性的损伤模式和基因表达变化相关，这些变化可以深入了解导致持续的结构和功能损伤的机制。早期的形态改变是由能量需求和氧气供应之间的微妙平衡驱动的，而这种平衡在肾脏的不同区域有很大的差异。不同肾单位节段的功能异质性反映在它们使用不同的代谢途径上。AKI 通常与肾脏氧气供应缺陷有关，一些肾单位在低氧条件下可能无法转向无氧代谢，或者可能具有极低的基础氧水平，这增加了它们受损的易感性。在这里，我们讨论为什么特定的肾脏区域特别容易受到损伤，以及这些信息如何帮助描绘出减轻损伤和避免永久性损伤的新途径。我们认为，在探索新的肾脏保护策略时，如改善肾脏组织氧合、刺激缺氧信号通路和调节细胞能量代谢，应考虑肾脏的生理异质性。
