An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients
An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients
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DOI：
10.1046/j.1523-1755.2002.00370.x
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发表时间：
2002-06-01
影响因子：
19.6
通讯作者：
Mauer, M
中科院分区：
文献类型：
--
作者：
Katz, A;Caramori, MLA;Mauer, M
背景。间质扩张在多种肾脏疾病的进展中很重要，包括糖尿病肾病（DN）。然而，构成 DN 间质扩张的间质成分尚不清楚，也是本报告的主题。方法。对 15 名长期患有 1 型糖尿病的患者进行了间质成分分析，其中 8 名患者皮层间质分数体积 [Vv(Int/cortex) 轻度增加（约为正常值的 1.5 倍），7 名患者中度增加（约为正常值的 2 倍）。轻度组年龄为 29 +/- 5（平均 +/- SD）岁，糖尿病病程为 17 +/- 5 年。中度组年龄较大（41 岁）。 +/- 7 年； P < 0.03），糖尿病病程较长（28 +/- 7 年；P = 0.002），肌酐清除率较低（90 +/- 14 mL/min/1.73 m(2) 对比 109 +/- 18 mL/min/1.73 m(2)；P = 0.05），并且更频繁地使用抗高血压药物（0/8 对比 4/7；P < 0.03）相比 轻度组。还对年龄和性别匹配的正常对照（N = 9）进行了研究。通过对在高 (x7500) 和低 (x1500) 放大倍率下无偏差系统获得的电子显微镜 (EM) 显微照片进行形态分析来评估间隙成分。结果。轻度间质扩张与间质细胞分数体积增加约 50% 相关 (P < 0.001) 间质核体积分数增加约 70% (P < 0.01)。这些患者间质细胞核的数量密度正常，表明间质细胞可能更大，而不仅仅是数量更多。当肌酐清除率已经达到正常水平时，仅在适度扩张时才观察到纤维胶原间质分数体积比正常值增加约 50% (P < 0.001)。 减少了。间质扩张与肾小管周围毛细血管体积和表面的减少以及毛细血管与肾小管表面比率的减少有关。结论。与基质积累起主导作用的早期系膜扩张相反，长期 1 型糖尿病患者的轻度间质扩张主要是由于间质细胞成分的增加。增加 间质纤维胶原的体积分数仅在疾病的后期阶段可见，此时肾小球滤过率已经降低。不同的发病过程可能在早期糖尿病肾小球和间质疾病中发挥作用。
Background. Interstitial expansion is important in the progression of a variety of kidney diseases, including diabetic nephropathy (DN). However, the interstitial elements that constitute interstitial expansion in DN are unknown and are the subject of this report.Methods. Interstitial composition was analyzed in 15 long-standing type 1 diabetic patients, 8 with mild (approximate to1.5 x normal) and 7 with moderate (approximate to2 x normal) increases in cortical interstitial fractional volume [Vv(Int/cortex]. The mild group was 29 +/- 5 (mean +/- SD) years old with diabetes duration of 17 +/- 5 years. The moderate group was older (41 +/- 7 years; P < 0.03), had longer diabetes duration (28 +/- 7 years; P = 0.002), lower creatinine clearance (90 +/- 14 mL/min/1.73 m(2) vs. 109 +/- 18 mL/min/1.73 m(2) ; P = 0.05) and used antihypertensive medications more frequently (0/8 vs. 4/7; P < 0.03) compared to the mild group. Age- and gender-matched normal controls (N = 9) also were studied. Interstitial composition was evaluated by morphometric analysis of electron microscopic (EM) micrographs systematically obtained without bias at high (x7500) and low (x1500) magnification.Results. Mild interstitial expansion was associated with an approximate to50% increase in fractional volume of interstitial cells (P < 0.001) and approximate to70% increase in fractional volume of interstitial nuclei (P < 0.01). Numerical density of interstitial nuclei was normal in these patients, suggesting that the interstitial cells might be larger rather than simply more numerous. An increase over normal in the interstitial fractional volume of fibrillary collagen of approximate to50% was seen only with moderate expansion (P < 0.001), when creatinine clearance was already decreased. Interstitial expansion was associated with a decrease in volume and surface of peritubular capillaries as well as with a reduction in surface ratio of capillaries to tubules.Conclusions. In contrast to early mesangial expansion where matrix accumulation plays a dominant role, mild interstitial expansion in long-standing type 1 diabetic patients is largely due to an increase in the cell component of the interstitium. Increased fractional volume of interstitial fibrillary collagen is only seen at later stages of the disease, when the glomerular filtration rate is already reduced. Different pathogenetic processes may be operative in early diabetic glomerular and interstitial diseases.