Schwartz M M, Evans J, Bidani A K
Department of Pathology, Rush Medical College, Chicago, IL.
J Lab Clin Med. 1994 Nov;124(5):644-51.
Hypertension, which develops during the course of the remnant kidney model (RK), plays a major role in the pathogenesis of glomerular injury. Morphologic studies have implicated mesangial injury and dysfunction in the pathogenesis of glomerular scarring in the hypertensive RK, but a separate role for mesangial injury has not been demonstrated in the absence of systemic hypertension. We studied glomerular injury and mesangial structure and function in a long-term (26 weeks) normotensive rat RK by using morphologic and morphometric studies and mesangial clearance of aggregated rate IgG (AggRaIgG). After right nephrectomy and infarction of two thirds of the left kidney (RK), the rats gained weight and developed mild but stable elevations of serum creatinine and urinary protein excretion as compared with the sham-operated controls (SHAM) over the course of the study. Systolic blood pressure was only mildly elevated (129 +/- 9 mm Hg versus 114 +/- 8 mm Hg, p < or = 0.05). Virtually all of the RK rats developed glomerular scarring, with segmental sclerosis in 8% +/- 8% and global sclerosis in 2% +/- 2% of the glomeruli, whereas the SHAM animals had no glomerular scarring, but we found limited morphologic evidence of mesangial cell injury in RK. The RK glomeruli were hypertrophied as compared with glomeruli in SHAM rats (glomerular diameter 199.3 +/- 15.2 microns versus 160.5 +/- 4.4 microns, p < or = 0.05), and the accompanying increase in capillary volume was caused by an increase in capillary length without a significant increase in diameter. Despite the glomerular hypertrophy and increased initial uptake in RK, the mesangial clearance of AggRaIgG was similar between RK and SHAM rats. We conclude that WKY rats with RK develop a progressive glomerulopathy characterized by segmental glomerulosclerosis, proteinuria, and mild hypertension. The normal mesangial clearance function and the absence of mesangial pathology in the hypertrophic remnant glomeruli mitigate against a role for mesangial injury in this form of experimental renal disease.
在残余肾模型（RK）病程中出现的高血压，在肾小球损伤的发病机制中起主要作用。形态学研究表明，在高血压RK模型中，肾小球系膜损伤和功能障碍与肾小球瘢痕形成的发病机制有关，但在无全身性高血压的情况下，尚未证实系膜损伤具有独立作用。我们通过形态学和形态计量学研究以及聚集率IgG（AggRaIgG）的系膜清除，对长期（26周）血压正常的大鼠RK模型中的肾小球损伤以及系膜结构和功能进行了研究。在右肾切除及左肾三分之二梗死（RK）后，与假手术对照组（SHAM）相比，在研究过程中，大鼠体重增加，血清肌酐和尿蛋白排泄出现轻度但稳定的升高。收缩压仅轻度升高（129±9mmHg对114±8mmHg，p≤0.05）。几乎所有的RK大鼠都出现了肾小球瘢痕形成，8%±8%的肾小球有节段性硬化，2%±2%的肾小球有全球性硬化，而SHAM组动物没有肾小球瘢痕形成，但我们在RK中发现了有限的系膜细胞损伤的形态学证据。与SHAM大鼠的肾小球相比，RK的肾小球肥大（肾小球直径199.3±15.2微米对160.5±4.4微米，p≤0.05），伴随的毛细血管容积增加是由毛细血管长度增加引起的，而直径没有显著增加。尽管RK中肾小球肥大且初始摄取增加，但RK和SHAM大鼠之间AggRaIgG的系膜清除相似。我们得出结论，患有RK的WKY大鼠会发展为以节段性肾小球硬化、蛋白尿和轻度高血压为特征的进行性肾小球病。肥厚的残余肾小球中正常的系膜清除功能以及系膜病理改变的缺失，排除了系膜损伤在这种实验性肾脏疾病中的作用。
