Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this "switch" must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.

了解肾单位丢失是预防 CKD 进展的主要策略。肾小管细胞的死亡可能在发育和再生过程中通过细胞凋亡发生。然而，在 AKI 期间，AKI 向 CKD 的转变、败血症相关的 AKI 以及肾移植铁死亡和细胞坏死，这两种与质膜完整性丧失相关的途径会杀死肾细胞。这种坏死类型的细胞死亡与炎症反应有关，称为坏死性炎症。重要的是，对因坏死性凋亡而死亡的细胞的坏死性炎症反应可能与组织对铁死亡的反应根本不同。尽管最近对铁死亡和细胞坏死的机制进行了详细研究，但肾小管坏死期间的细胞死亡传播，尽管在形态学上有所描述，仍然不完全理解。在这里，我们认为肾小管坏死下游的分子开关决定了肾单位再生与肾单位损失。解开这个“开关”的细节必须包括对肾小管坏死的炎症反应和可能由炎症细胞控制的再生信号，包括作为纤维化起源的肌成纤维细胞的刺激。详细了解分子开关和对肾小管坏死的炎症反应可以为治疗方案的讨论提供信息。必须包括对肾小管坏死的炎症反应和可能由炎症细胞控制的再生信号，包括作为纤维化起源的肌成纤维细胞的刺激。详细了解分子开关和对肾小管坏死的炎症反应可以为治疗方案的讨论提供信息。必须包括对肾小管坏死的炎症反应和可能由炎症细胞控制的再生信号，包括作为纤维化起源的肌成纤维细胞的刺激。详细了解分子开关和对肾小管坏死的炎症反应可以为治疗方案的讨论提供信息。