Lund Ulla, Rippe Anna, Venturoli Daniele, Tenstad Olav, Grubb Anders, Rippe Bengt
Department of Nephrology, University Hospital, S-221 85 Lund, Sweden.
Am J Physiol Renal Physiol. 2003 Jun;284(6):F1226-34. doi: 10.1152/ajprenal.00316.2002. Epub 2003 Mar 4.
The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs. glomerular filtration rate (GFR; (51)Cr-EDTA clearance) in intact rats for radiolabeled myoglobin, kappa-dimer, neutral horseradish peroxidase (nHRP), neutral human serum albumin (nHSA), and native albumin (HSA). To obtain theta, glomerular tracer clearance, assessed from the 7- to 8-min kidney uptake of protein, was divided by the GFR. The data were fitted with a two-pore model of glomerular permeability, where the small-pore radius was 37.35 +/- 1.11 (SE) A, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 x 10(6) cm. Although seemingly horizontal for nHRP and nHSA, the log theta vs. GFR curves showed slightly negative slopes for the proteins investigated in the GFR interval of 2-4.5 ml/min. Strong negative (linear) correlations between (log) theta and GFR were obtained for myoglobin (P = 0.002) and HSA (P = 0.006), whereas they were relatively weak for nHRP and nHSA and nonsignificant for kappa-dimer. Theta for nHSA was markedly higher than that for HSA. In conclusion, there were no indications of increases in theta vs. GFR, as indicative of concentration polarization, for the proteins investigated at high GFRs. Furthermore, the glomerular small-pore radius assessed from endogenous (neutral) protein sieving data was found to be smaller than previously determined using dextran or Ficoll as test molecules.
肾小球屏障的大小和电荷选择性特性存在一定争议。此前，蛋白质的肾小球滤过系数（θ）在体内很少通过非侵入性方法测定。因此，在完整大鼠中，针对放射性标记的肌红蛋白、κ二聚体、中性辣根过氧化物酶（nHRP）、中性人血清白蛋白（nHSA）和天然白蛋白（HSA），评估了θ与肾小球滤过率（GFR；（51）Cr - EDTA清除率）的关系。为获得θ，根据7至8分钟肾脏对蛋白质的摄取量评估的肾小球示踪剂清除率除以GFR。数据采用肾小球通透性的双孔模型进行拟合，其中小孔半径为37.35±1.11（SE）埃，“扩散路径长度上的无限制孔面积”（A(0)/ΔX）为1.84±0.43×10(6)平方厘米。尽管nHRP和nHSA的对数θ与GFR曲线看似水平，但在2 - 4.5毫升/分钟的GFR区间内，所研究蛋白质的对数θ与GFR曲线显示出轻微的负斜率。肌红蛋白（P = 0.002）和HSA（P = 0.006）的（对数）θ与GFR之间存在强负（线性）相关性，而nHRP和nHSA的相关性相对较弱，κ二聚体的相关性不显著。nHSA的θ明显高于HSA。总之，在高GFR下所研究的蛋白质中，没有迹象表明θ随GFR增加，这表明不存在浓度极化现象。此外，根据内源性（中性）蛋白质筛分数据评估的肾小球小孔半径比先前使用葡聚糖或菲可用于测试分子时确定的要小。
