Tabei K, Levenson D J, Brenner B M
J Clin Invest. 1983 Sep;72(3):871-81. doi: 10.1172/JCI111058.
To assess the renal functional adaptation to reduced excretory capacity, we studied whole kidney and single nephron function in anesthetized volume-replete rabbits after unilateral (left kidney) nephrectomy (UNX), ureteral obstruction (UO), or ureteroperitoneostomy (UP). At 24 h, despite the absence of measurable hypertrophy of the contralateral (right) kidney, these procedures significantly increased p-aminohippurate clearance (45-54%) and inulin clearance (CIN) (64-110%) compared with sham-operated control animals. In each group, whole kidney sodium reabsorption increased in proportion to the rise in CIN. To determine whether the intrinsic transport capacity of proximal tubule segments is altered by these maneuvers, we measured fluid volume reabsorption rate (Jv) in isolated superficial proximal straight tubule (PST) segments perfused in vitro, comparing each control tubule (obtained by biopsy of the left kidney immediately before an experimental maneuver) with a corresponding tubule segment obtained 24 h or 7 d later from the contralateral kidney. Control tubule Jv in sham-24 h animals averaged 0.48 +/- 0.04 nl/(min X mm). Jv did not change significantly at 24 h or 7 d after sham maneuvers but increased significantly at 24 h after UNX [delta Jv = 0.13 +/- 0.03 nl/(min X mm)], UO [delta Jv = 0.10 +/- 0.04 nl/(min X mm)], and UP [delta Jv = 0.13 +/- 0.04 nl/(min X mm)]. Jv remained increased by similar amounts at 7 d after UNX and UO. To evaluate whether an increase in glomerular filtration rate (GFR) might be the stimulus to this augmentation in Jv values, methylprednisolone (MP) (15 mg/kg per d) was administered daily to sham-operated animals, a maneuver which induced a 73% rise in CIN by day 5. This procedure also produced a significant increase in Jv in PST at 5 d [delta Jv = 0.16 +/- 0.05 nl/(min X mm)]. The increase in Jv evident in each group at 5 or 7 d was paralleled by an equivalent change in tubule cell volume and apparent tubule luminal surface area in UNX-7d and MP-5d; no such increments in these indices, or in apparent tubule serosal surface area were evident at 24 h in any group. Thus, a 50% reduction in renal excretory function in the rabbit provokes adjustments in renal plasma flow rate and GFR in the contralateral kidney, which are evident by 24 h. The concurrent change in Jv in PST is closely related to CIN or some associated hemodynamic process, but does not appear to require an increase in tubule cell volume or apparent surface area. The ability to detect these small in vivo changes in Jv may derive from the enhanced sensitivity of paired-kidney experiments using tubule segments obtained by renal biopsy.
为评估肾脏功能对排泄能力降低的适应性,我们在单侧(左肾)肾切除(UNX)、输尿管梗阻(UO)或输尿管腹膜造口术(UP)后,对麻醉状态下血容量充足的家兔的全肾和单肾单位功能进行了研究。术后24小时,尽管对侧(右)肾无明显可测的肥大,但与假手术对照组动物相比,这些手术显著增加了对氨基马尿酸盐清除率(45 - 54%)和菊粉清除率(CIN)(64 - 110%)。在每组中,全肾钠重吸收与CIN的升高成比例增加。为确定这些操作是否改变近端小管节段的内在转运能力,我们在体外灌注的分离浅表近端直小管(PST)节段中测量了液体体积重吸收率(Jv),将每个对照小管(在实验操作前立即从左肾活检获得)与24小时或7天后从对侧肾获得的相应小管节段进行比较。假手术24小时组动物的对照小管Jv平均为0.48±0.04 nl/(min×mm)。假手术后24小时或7天Jv无显著变化,但在UNX术后24小时[ΔJv = 0.13±0.03 nl/(min×mm)]、UO术后24小时[ΔJv = 0.10±0.04 nl/(min×mm)]和UP术后24小时[ΔJv = 0.13±0.04 nl/(min×mm)]Jv显著增加。UNX和UO术后7天Jv仍有相似幅度的增加。为评估肾小球滤过率(GFR)的增加是否可能是Jv值升高的刺激因素,每天给假手术动物注射甲泼尼龙(MP)(15 mg/kg),该操作在第5天时使CIN升高73%。此操作在第5天时也使PST中的Jv显著增加[ΔJv = 0.16±0.05 nl/(min×mm)]。在UNX - 7天和MP - 5天组中,第5天或7天每组中明显的Jv增加与小管细胞体积和明显的小管腔表面积的同等变化平行;在任何组的24小时时,这些指标或明显的小管浆膜表面积均无此类增加。因此,家兔肾脏排泄功能降低50%会引起对侧肾肾血浆流速和GFR的调整,在24小时时即可明显观察到。PST中Jv的同时变化与CIN或某些相关的血流动力学过程密切相关,但似乎不需要小管细胞体积或明显表面积的增加。检测Jv这些小的体内变化的能力可能源于使用肾活检获得的小管节段进行的双肾实验的增强敏感性。