Eppel G A, Osicka T M, Pratt L M, Jablonski P, Howden B O, Glasgow E F, Comper W D
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Kidney Int. 1999 May;55(5):1861-70. doi: 10.1046/j.1523-1755.1999.00424.x.
Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high, and this has been confirmed in studies in which albumin uptake by the tubules has been inhibited. Therefore, there must be a high-capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply.
This study identifies the presence of glomerular-filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium-labeled albumin into the renal artery in vivo and in the isolated perfused kidney.
The postglomerular filtered albumin is returned to the blood supply by a high-capacity pathway that transports this albumin at a rate of 1830 +/- 292 micrograms/min.rat kidney (N = 14, mean +/- SEM). This pathway has been identified under physiological conditions in vivo and in the isolated perfused kidney. The pathway is specific for albumin, as it does not occur for horseradish peroxidase. The pathway is inhibited in a nonfiltering kidney. The pathway is also inhibited by ammonium chloride (an agent that inhibits tubular protein uptake but does not alter glomerular size selectivity) and by albumin peptides (which compete for the tubular albumin receptor).
The high-capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.
最近的研究表明,正常的肾小球毛细血管壁(GCW)对白蛋白没有电荷选择性。这意味着白蛋白通过GCW的通量很高,这在肾小管对白蛋白摄取受到抑制的研究中得到了证实。因此,正常肾脏中必定存在一条高容量的肾小球后重吸收途径,可将滤过的白蛋白返回血液循环。
本研究通过分析体内将脉冲氚标记白蛋白注入肾动脉后静脉流出物中放射性的降低情况,以及在离体灌注肾中的情况,来确定肾静脉中是否存在肾小球滤过的白蛋白。
肾小球后滤过的白蛋白通过一条高容量途径返回血液循环,该途径以1830±292微克/分钟·大鼠肾脏的速率转运白蛋白(N = 14,平均值±标准误)。此途径已在体内生理条件下以及离体灌注肾中得到确认。该途径对白蛋白具有特异性,因为辣根过氧化物酶不会出现这种情况。在无滤过功能的肾脏中该途径受到抑制。氯化铵(一种抑制肾小管蛋白摄取但不改变肾小球大小选择性的试剂)和白蛋白肽(与肾小管白蛋白受体竞争)也会抑制该途径。
白蛋白的高容量重吸收途径很可能与跨肾小管细胞转运有关。同样明显的是,大多数蛋白尿状态可能是由于该途径功能失调所致,而无需肾小球通透选择性发生任何改变。