Chevalier Robert L, Forbes Michael S
Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA 22908, USA.
J Am Soc Nephrol. 2008 Feb;19(2):197-206. doi: 10.1681/ASN.2007080862. Epub 2008 Jan 16.
Functional nephrons can be lost through a process of glomerulotubular disconnection. Progressive development of atubular glomeruli seems to play a major role in a number of renal disorders, including glomerular diseases, ascribed to injury to the glomerulotubular junction as a result of proteinuria; however, formation of atubular glomeruli is even more common in tubulointerstitial disorders, such as obstructive nephropathy. Toxic nephropathy is also associated with the formation of atubular glomeruli, suggesting susceptibility of the glomerulotubular junction to toxic injury. Narrowing or other abnormalities of the glomerulotubular junction are described as precursors of glomerulotubular disconnection. Cystinosis represents a dramatic example of progressive injury to the glomerulotubular junction, with formation of the "swan-neck deformity" following degenerative tubular cell changes attributable to apoptosis. Significant numbers of atubular glomeruli have been reported in chronic pyelonephritis and renal allograft rejection; this suggests interstitial inflammation as a stimulus for the formation of atubular glomeruli. Because of difficulties in morphologic recognition, it is likely that glomerulotubular disconnection is an underappreciated mechanism in the progression of renal disease. A better understanding of the vulnerability of the glomerulotubular junction and its protection from injury should lead to better strategies for preserving renal function in many nephropathies.
功能性肾单位可通过肾小球肾小管分离的过程而丧失。无肾小管肾小球的逐渐发展似乎在包括肾小球疾病在内的多种肾脏疾病中起主要作用，这些疾病归因于蛋白尿导致的肾小球肾小管连接损伤；然而，无肾小管肾小球的形成在肾小管间质疾病如梗阻性肾病中更为常见。中毒性肾病也与无肾小管肾小球的形成有关，提示肾小球肾小管连接对毒性损伤敏感。肾小球肾小管连接变窄或其他异常被描述为肾小球肾小管分离的先兆。胱氨酸病是肾小球肾小管连接进行性损伤的一个显著例子，由于凋亡导致肾小管细胞变性后形成“天鹅颈畸形”。慢性肾盂肾炎和肾移植排斥反应中已报道有大量无肾小管肾小球；这提示间质炎症是无肾小管肾小球形成的刺激因素。由于形态学识别存在困难，肾小球肾小管分离很可能是一种在肾脏疾病进展中未得到充分认识的机制。更好地了解肾小球肾小管连接的易损性及其免受损伤的保护机制，应能为许多肾病中保护肾功能带来更好的策略。
