After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma, and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this failed-repair proximal tubule cell (FR-PTC) state can be detected in other models of kidney injury, increasing during aging in rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.

急性肾损伤（AKI）后，患者要么康复，要么发展为纤维化和慢性肾病。受损的上皮、间质和炎症细胞之间的相互作用决定肾脏是否修复或发生纤维化，但驱动这些过程的分子事件却知之甚少。在这里，我们使用 AKI 小鼠模型的单核 RNA 测序来表征急性损伤修复过程中的细胞状态。我们发现了一种无法修复的独特的促炎和促纤维化近曲小管细胞状态。大量 RNA-seq 数据集的反卷积表明，这种修复失败的近端小管细胞 (FR-PTC) 状态可以在其他肾损伤模型中检测到，在大鼠肾脏的衰老过程中以及在人肾同种异体移植物中随着时间的推移而增加。我们还描述了动态细胞间通讯网络，并辨别驱动成功修复和失败修复的转录途径。我们的研究提供了损伤后细胞反应的详细描述，并表明 FR-PTC 状态可能代表改善修复的治疗目标。