Nature Reviews Nephrology ( IF 28.6 ) Pub Date : 2024-04-17 , DOI: 10.1038/s41581-024-00834-0 Christian Hinze 1 , Svjetlana Lovric 1 , Philip F Halloran 2, 3 , Jonathan Barasch 4 , Kai M Schmidt-Ott 1
The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes. However, epithelial injury is currently neither monitored clinically nor addressed therapeutically after kidney transplantation. Several factors can contribute to allograft epithelial injury, including allograft rejection, drug toxicity, recurrent infections and postrenal obstruction. The injury mechanisms that underlie allograft injury overlap partially with those associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in the native kidney. Studies using advanced transcriptomic analyses of single cells from kidney or urine have identified a role for kidney injury-induced epithelial cell states in exacerbating and sustaining damage in AKI and CKD. These epithelial cell states and their associated expression signatures are also observed in transplanted kidney allografts, suggesting that the identification and characterization of transcriptomic epithelial cell states in kidney allografts may have potential clinical implications for diagnosis and therapy.
中文翻译:
与肾脏和同种异体移植物损伤相关的上皮细胞状态
肾上皮细胞错综复杂,由高度特化的细胞类型组成,构成了器官的功能核心。肾上皮的丧失与功能性肾单位的丧失和随后的肾功能下降有关。在肾移植中,移植后监测期间观察到的上皮损伤特征是不良肾同种异体移植结局的强预测因子。然而,肾移植后上皮损伤目前既没有临床监测,也没有治疗性解决。有几个因素可导致同种异体移植物上皮损伤,包括同种异体移植物排斥反应、药物毒性、复发性感染和肾后梗阻。同种异体移植物损伤的损伤机制与自体肾急性肾损伤 (AKI) 和慢性肾病 (CKD) 相关的损伤机制部分重叠。使用肾脏或尿液中单细胞的高级转录组学分析的研究已经确定了肾损伤诱导的上皮细胞状态在加剧和维持 AKI 和 CKD 损伤中的作用。在移植的同种异体肾移植物中也观察到这些上皮细胞状态及其相关的表达特征,这表明肾同种异体移植物中转录组上皮细胞状态的鉴定和表征可能对诊断和治疗具有潜在的临床意义。