Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation
Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation
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DOI：
10.1046/j.1523-1755.2003.00831.x
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发表时间：
2003-03-01
影响因子：
19.6
通讯作者：
Bariéty, J
中科院分区：
文献类型：
--
作者：
Hill, GS;Heudes, D;Bariéty, J
背景。在过去，人们普遍认为透明质传入小动脉硬化是导致衰老和高血压肾缺血性肾小球硬化的原因。然而，局灶节段性肾小球硬化的肾小球病变现在被认为是原发性高血压。实验表明，这种病变与血流自我调节功能丧失和肾小球高灌注以及初始肾小球肥大有关。这些观察结果挑战了缺血作为肾小球硬化的单一解释的概念。形态学计量学研究对衰老、血压正常的患者因肿瘤切除的8个肾脏的正常部分进行了研究。测量126对传入小动脉及其相关的肾小球。同时定量测定大鼠肾小球周围细胞外基质（ECM）的含量。根据是否存在透明质沉积物以及是否阻塞管腔，将传入小动脉分为三种类型。非阻塞性透明样沉积的小动脉的管腔是无沉积的小动脉的两倍多(482 +/- 240 mu（2) vs. 204 +/- 160 mu(2), P = 0.0000）。其相关肾小球的总毛细血管面积显着增加，特别是门部毛细血管(1276 +/- 797亩（2)vs. 667 +/- 492亩(2),P = 0.002），但其他地方的毛细血管也更大（P = 0.03）。梗阻性沉积物的小动脉与非梗阻性沉积物的不同之处在于其管腔（P = 0.001）和壁（P = 0.004）更小，肾小球周围区域ECM比例更高（P = 0.001），所有这些都与病变晚期相一致。肾小球分为四种基本类型：正常型、肥厚型、以局灶节段性肾小球硬化（fsgs型）为特征的肾小球和缺血性肾小球。与正常肾小球相比，增生性肾小球体积更大，毛细血管总面积更大（P = 0.0005），尤其是肾门毛细血管（P = 0.0000），其余部分毛细血管面积更大（P = 0.003），但未见明显病变。fsgs型肾小球也更大，肾小球门部毛细血管更大（P = 0.0005），但由于硬化病变导致ECM增加（P = 0.004）。剩余的毛细血管与系膜基质的数量呈反比关系，显示出从增大到缩小的大小谱。正如预期的那样，缺血肾小球在各项指标上都明显小于正常肾小球。肥厚型/ fsgs型肾小球与透明小动脉硬化之间存在很强的相关性，90.3%的此类肾小球存在这种相关性，其余肾小球存在29.1%的相关性（P = 0.0001）。绝大多数透明质沉积是非梗阻性的（86.2%），但也有一些是梗阻性的（13.8%），特别是在fsgs型肾小球中，与更晚期的病变一致。我们相信，我们已经在人类衰老肾脏中证明了自调节丧失的形态学相关性，它发生在局灶性基础上，伴随着传入小动脉扩张和肾小球毛细血管大小的增加，以及随后的局灶节段性肾小球硬化。非阻塞性透明小动脉硬化与这些变化密切相关，并可能在其发病机制中发挥作用。
Background. In the past it was widely assumed that hyaline afferent arteriolosclerosis was responsible for ischemic glomerulosclerosis in the aging and hypertensive kidney. However, glomerular lesions of focal segmental glomerulosclerosis are now recognized in essential hypertension. Experimentally, such lesions are associated with loss of autoregulation of blood flow and glomerular hyperperfusion, as well as initial glomerular hypertrophy. These observations challenge the notion of ischemia as a unitary explanation for glomerulosclerosis.Methods. A morphometric study was performed on normal portions of eight kidneys removed for tumors in aging, normotensive patients. Measurements were made of 126 pairs of afferent arterioles and their associated glomeruli. In addition, the amount of extracellular matrix (ECM) in the immediate periglomerular region was quantitated.Results. Afferent arterioles were divided into three types according to the presence or absence of hyaline deposits and whether these did or did not obstruct the lumen. Arterioles with nonobstructive hyaline deposits had lumens over twice as large as those without deposits (482 +/- 240 mu(2) vs. 204 +/- 160 mu(2) , P = 0.0000). Their associated glomeruli had significantly greater total capillary area, particularly the hilar capillaries (1276 +/- 797 mu(2) vs. 667 +/- 492 mu(2) , P = 0.002), but with larger individual capillaries elsewhere as well (P = 0.03). Arterioles with obstructive deposits differed from those with nonobstructive deposits by their smaller lumens (P = 0.001) and walls (P = 0.004), with a higher proportion of ECM in the periglomerular region (P = 0.001), all consistent with a later stage of lesion. Glomeruli were divided into four basic types: normal, hypertrophic, glomeruli with features of focal segmental glomerulosclerosis (FSGS-type), and ischemic. Compared to normal glomeruli, hypertrophic glomeruli were larger, with greater total capillary area (P = 0.0005), particularly the hilar capillaries (P = 0.0000), and larger capillaries in the remainder of the tuft (P = 0.003), but showed no evident lesions. FSGS-type glomeruli were also larger, with larger hilar capillaries (P = 0.0005), but showed an increase in ECM due to sclerotic lesions (P = 0.004). The remaining capillaries showed an inverse relation with the amount of mesangial matrix, showing a spectrum of sizes from enlarged to shrunken. As anticipated, ischemic glomeruli were significantly smaller than normal ones in every parameter measured. There was a strong association between hypertrophic/FSGS-type glomeruli and hyaline arteriolosclerosis, found in 90.3% of such glomeruli, versus 29.1% for the remaining glomeruli (P = 0.0001). The great majority of hyaline deposits were of the nonobstructive variety (86.2%), but some were obstructive (13.8%), particularly in FSGS-type glomeruli, consistent with a more advanced lesion.Conclusions. We believe we have demonstrated in the aging kidney of humans the morphologic correlates of loss of autoregulation, occurring on a focal basis, with afferent arteriolar dilatation and increase in glomerular capillary size and subsequent focal segmental glomerulosclerosis. Hyaline arteriolosclerosis of the nonobstructive sort is strongly associated with these changes and may play a role in their pathogenesis.