Geis Lisa, Kurtz Armin
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Institute of Physiology, University of Regensburg, Regensburg, Germany.
Nephrol Dial Transplant. 2025 Feb 28;40(3):446-454. doi: 10.1093/ndt/gfae225.
The kidneys fulfil several essential homeostatic functions for the body. One of them is the maintenance of sufficient oxygen supply to the organs. For this purpose, the kidneys control the formation of red blood cells by the production of the hormone erythropoietin. This control of red cell formation is not only relevant to prevent states of oxygen deficiency but also to prevent an unwanted increase of red cell numbers causing thromboembolic risks. The adequate production of erythropoietin requires a sensing of the arterial oxygen content and transduction to hormone production. This oxygen sensing is a two-step process which includes a translation of the arterial oxygen content to respective oxygen tension in the tubulointerstitium and a perception of the resulting local interstitial oxygen tension to translate them into specific cellular responses such as the production of erythropoietin. This contribution will describe these steps of oxygen sensing for the healthy kidney and for the changes occurring during states of chronic renal disease, which are commonly associated with anemia. In this context a special focus will also be set on intrarenal hypoxia and oxygen sensing in the diabetic kidney including the treatment with tubular glucose transport (sodium-glucose cotransporter 2) inhibitors which might influence the oxygen sensing in the kidney. Finally, we will consider the effects of prolyl-hydroxylase inhibitors (HIF-PHIs), which fundamentally interfere with the cellular oxygen sensing and which are meanwhile treatment options in renal anemia.
肾脏为身体履行多种重要的稳态功能。其中之一是维持器官充足的氧气供应。为此，肾脏通过产生促红细胞生成素激素来控制红细胞的生成。这种对红细胞生成的控制不仅与预防缺氧状态有关，还与防止红细胞数量不必要的增加导致血栓栓塞风险有关。促红细胞生成素的充分产生需要感知动脉血氧含量并将其转化为激素生成。这种氧感知是一个两步过程，包括将动脉血氧含量转化为肾小管间质中的相应氧张力，以及感知由此产生的局部间质氧张力，将其转化为特定的细胞反应，如促红细胞生成素的产生。本文将描述健康肾脏以及慢性肾病状态下发生的变化（通常与贫血相关）的氧感知这些步骤。在此背景下，还将特别关注糖尿病肾病中的肾内缺氧和氧感知，包括使用肾小管葡萄糖转运（钠-葡萄糖协同转运蛋白2）抑制剂进行治疗，这可能会影响肾脏的氧感知。最后，我们将考虑脯氨酰羟化酶抑制剂（HIF-PHIs）的作用，它们从根本上干扰细胞氧感知，同时也是肾性贫血的治疗选择。
