Wedeen R P
Am J Med. 1977 Feb;62(2):243-51. doi: 10.1016/0002-9343(77)90320-5.
In vitro concentrative transport to tritiated p-aminohippuric acid (3H-PAH) was evaluated in renal biopsy specimens from human subjects by section freeze-dry autoradiography. Renal cortical tissue obtained by percutaneous needle biopsy (23 of 27 tissue specimens) was incubated in vitro using a modified renal cortical slice technic. Following incubation in medium containing 3H-PAH, the biopsy fragment was snap-frozen, and section freeze-dry autoradiographs were prepared. The autoradiographs demonstrated cellular accumulation of 3H-PAH by proximal tubules of human kidney in vitro and suggest that PAH transport is uphill across the luminal as well as the antiluminal membrane. The number of proximal tubules which accumulate 3H-PAH in vitro diminishes as renal failure progresses. Cellular accumulation of PAH, however, was not impaired by heavy proteinuria, and appeared not to be related to the underlying glomerular histologic diagnosis. The frequency of proximal tubules showing 3H-PAH uptake in the cortex varied directly with the glomerular filtration rate and inversely with the degree of interstitial involvement. Proximal tubules which maintain the ability to accumulate 3H-PAH are clustered in fewer regions of the cortex in patients with reduced glomerular filtration rates. This observation is consistent with the view that residual renal function is renal failure arises from a few relatively normal nephrons rather than from a more uniformly damaged population of nephrons.
通过切片冷冻干燥放射自显影术,对人类受试者肾活检标本中对氚标记对氨基马尿酸(3H-PAH)的体外浓缩转运进行了评估。采用改良的肾皮质切片技术,对经皮穿刺活检获取的肾皮质组织(27个组织标本中的23个)进行体外孵育。在含有3H-PAH的培养基中孵育后,将活检组织块速冻,并制备切片冷冻干燥放射自显影片。放射自显影片显示,人肾近端小管在体外对3H-PAH有细胞内蓄积,提示PAH转运是跨管腔膜和反管腔膜的上坡转运。随着肾衰竭进展,体外蓄积3H-PAH的近端小管数量减少。然而,PAH的细胞内蓄积不受重度蛋白尿影响,且似乎与潜在的肾小球组织学诊断无关。皮质中显示摄取3H-PAH的近端小管频率与肾小球滤过率直接相关,与间质受累程度呈负相关。肾小球滤过率降低的患者中,保持蓄积3H-PAH能力的近端小管聚集在皮质较少的区域。这一观察结果与以下观点一致,即肾衰竭时残余肾功能源于少数相对正常的肾单位,而非源于更均匀受损的肾单位群体。