MECHANISMS OF FILTRATION FAILURE DURING POSTISCHEMIC INJURY OF THE HUMAN KIDNEY - A STUDY OF THE REPERFUSED RENAL-ALLOGRAFT
MECHANISMS OF FILTRATION FAILURE DURING POSTISCHEMIC INJURY OF THE HUMAN KIDNEY - A STUDY OF THE REPERFUSED RENAL-ALLOGRAFT
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DOI：
10.1172/jci117732
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发表时间：
1995-02-01
影响因子：
15.9
通讯作者：
MYERS, BD
中科院分区：
文献类型：
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作者：
ALEJANDRO, V;SCANDLING, JD;MYERS, BD
实验动物中的缺血后滤过失败主要是由于跨毛细血管液压差（Δ P）的降低，这是一个无法在人体中确定的量。为了规避这一限制，我们测定了移植肾的GFR及其其余决定因素。将12例表现出后续正常滤过的同种异体移植物（第1组）的结果与11例表现出持续低滤过的同种异体移植物（第2组）的结果进行比较。再灌注1-3小时后，在暴露的移植物中进行术中测定。GFR（6 +/- 2 vs 29 +/- 5 ml/min）和肾血浆流量（多普勒流量计）（140 +/- 30 vs 315 +/- 49 ml/min）显著低于第1组。通过活检和粘性流的结构流体动力学模型获得的肾小球形态计量学分析显示肾小球超滤系数相似，第2组与第1组的平均值分别为3.5 +/- 0.6和3.1 +/- 0.2 ml/（min.mmHg）。血浆onset压的相应值也相似，平均值为19 +/- 1 vs 21 +/- 1 mmHg。接下来，我们使用肾小球超滤的数学模型和灵敏度分析来计算来自前述测量量的Δ P的主要范围。这表明第2组中的Δ P仅为20-21 mmHg，而第1组为34-45 mmHg（P < 0.001）。进一步的形态学分析显示，Bowman间隙和管腔的直径以及坏死或缺乏刷状缘的肾小管细胞的百分比在两组中相似。因此，我们得出结论：（a）Delta P抑制是这种缺血后损伤形式的低滤过的主要原因;（B）传入血管收缩而不是肾小管阻塞是Delta P抑制的近因。
Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (Delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler how meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1, Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for Delta P from the foregoing measured quantities. This revealed Delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that Delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the Delta P depression.