Chronic injury of human renal microvessels with low-dose cyclosporine therapy.
Chronic injury of human renal microvessels with low-dose cyclosporine therapy.
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小剂量环孢素治疗对人肾微血管的慢性损伤。
DOI：
10.1097/00007890-198811000-00014
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发表时间：
1988
期刊：
影响因子：
6.2
通讯作者：
Sibley,RK
中科院分区：
文献类型：
--
作者：
Myers,BD;Newton,L;Boshkos,C;Macoviak,JA;Frist,WH;Derby,GC;Perlroth,MG;Sibley,RK
生理学和形态学技术被用来研究心脏移植受者的肾脏，无论是低剂量（低CsA）或高剂量（高CsA）环孢素治疗。12个月后，低CsA（4.6±0.4）和高CsA（6.3±0.3 mg/Kg/24 hr，p< 0.01）均与氮质血症和高血压相关;在未接受CsA治疗的第三组（无CsA）中，每种方案的GFR均降低至低于数值40- 47%，而相应的肾血管阻力升高> 2倍（P< 0.01）。两个CsA组的形态学变化包括闭塞性小动脉病伴下游肾小球塌陷或硬化。肾弓状静脉闭塞压力的测定显示，CsA治疗1至12个月之间，肾动脉至肾小管周围毛细血管压力梯度增加。与无CsA组相比，分级大小的葡聚糖的清除率分数在每个时间点均升高。用等孔膜模型对葡聚糖转运的分析表明，无CsA时的跨肾小球液压差（AP）约为39，但低CsA治疗后1个月时降低至约30，12个月后约为34 mmHg。我们的结论是，慢性CsA治疗诱导收缩和最终闭塞的传入小动脉，造成下游肾小球损伤是不可逆的。低剂量与高剂量的CsA仅对这种严重的微血管损伤提供边缘保护。
Physiologic and morphologic techniques were used to study kidneys of cardiac transplant recipients treated with either low-dose (low-CsA) or high-dose (high-CsA) cyclosporine. After 12 months both low-CsA (4.6±0.4) and high-CsA (6.3±0.3 mg/Kg/24 hr, p< 0.01) were associated with azotemia and hypertension; GFR with each regimen was depressed below values in a third group treated without CsA (no-CsA) by 40–47%, while corresponding renal vascular resistance was elevated> 2-fold (P< 0.01). Morphologic changes in both CsA groups included an obliterative arteriolopathy with downstream collapse or sclerosis of glomeruli. Determination of renal arcuate vein occlusion pressure revealed an increasing renal artery-to-peritubular capillary pressure gradient between 1 and 12 months of CsA therapy. Fractional clearances of dextrans of graded size were elevated at each time compared with the no-CsA group. Analysis of dextran transport with an isoporous membrane model indicates that transglomerular hydraulic pressure difference (AP) approximated 39 with no-CsA, but was reduced with low-CsA therapy to about 30 at 1 month, and about 34 mmHg after 12 months. We conclude that chronic CsA therapy induces constriction and eventual occlusion of afferent arterioles, causing downstream glomerular damage that is irreversible. Low versus high dosage of CsA confers only marginal protection against this serious microvascular injury.