The Tubulointerstitial Pathophysiology of Progressive Kidney Disease.
The Tubulointerstitial Pathophysiology of Progressive Kidney Disease.
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DOI：
10.1053/j.ackd.2016.11.011
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发表时间：
2017-03
影响因子：
2.9
通讯作者：
Schnaper HW
中科院分区：
文献类型：
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作者：
Schnaper HW
越来越多的证据表明，慢性肾脏疾病（CKD）进展的中心位点是肾近端小管。当受损的肾小管上皮细胞在试图修复时去分化，它们刺激炎症并招募肌成纤维细胞。与此同时，组织损失刺激残余肾单位肥大。增加的肾小管转运工作量最终超过肥大肾单位的能量产生能力，导致无氧代谢、酸中毒、缺氧、内质网应激和诱导额外的炎症和纤维化反应。其结果是一个恶性循环的损伤，错误的修复，适应不良的反应和更多的肾单位损失。在该进展途径的一个阶段可能有利的治疗在其他阶段可能有害。因此，中断这种螺旋式下降需要有针对性的方法，以促进愈合和充分的功能，而不会进一步进入进展周期。
Accumulating evidence suggests that the central locus for the progression of chronic kidney disease (CKD) is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.