Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine
Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine
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DOI：
10.1046/j.1523-1755.2001.00491.x
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发表时间：
2001-01-01
影响因子：
19.6
通讯作者：
Matzke, GR
中科院分区：
文献类型：
--
作者：
Dowling, TC;Frye, RF;Matzke, GR
背景。肾小球滤过和主动肾小管分泌的肾脏药物排泄可能会因急性和慢性肾脏疾病、肾毒素和药物相互作用等因素而改变。因此，准确且可重复的肾小球滤过率 (GFR) 和肾小管功能容量定量方法至关重要。我们采用四步顺序输注方法来表征健康志愿者的阴离子[对氨基马尿酸 (PAH)I 和阳离子（法莫替丁）肾小管功能能力。通过肾清除率和碘酞酸盐衍生的 GFR 测定来定量过滤和分泌率。结果。当血浆浓度 >100 mg/L 时，观察到 PAH 的浓度依赖性肾清除率；在血浆浓度为 18 +/- 2、92 +/- 5、291 +/- 47 和 789 +/- 28 mg/L 时，肾清除率分别为 442 +/- 131（平均值 +/- SD）、423 +/- 94、233 +/- 45 和 152 +/- 18 mL/min/1.73 m(2)。表观亲和力 (K-m) 和最大分泌能力 (Tm-PAH) 分别为 141 +/- 70 mg/L 和 71 +/- 16 mg/min/1.73 m(2)。法莫替丁的未结合肾清除率和肾小管分泌清除率分别为384 +/- 70和329 +/- 78 mL/min/1.73 m(2)，与未结合血浆浓度（范围为126至2659 ng/mL）没有显着相关性。在未结合血浆浓度高达 2659 ng/mL 时，肾小管分泌率呈线性。结论。这些数据表明，使用 PAH 的顺序输注方法可用于表征近端肾小管功能的阴离子分泌成分。法莫替丁的肾小管清除率可能是人体近曲小管阳离子分泌能力的合适指标。没有观察到阳离子分泌途径的饱和，并且可能需要进一步研究阳离子分泌的平行途径，例如p-糖蛋白。
Background. Renal drug excretion by glomerular filtration and active tubular secretion may be altered by factors such as acute and chronic renal disease, nephrotoxins, and drug interactions. Thus, accurate and reproducible methods for quantitation of glomerular filtration rate (GFR) and tubular functional capacity are critical.Methods. We utilized a four-step sequential infusion method to characterize anionic [para-aminohippurate (PAH)I and cationic (famotidine) tubular functional capacity in healthy volunteers. Filtration and secretion rates were quantitated from renal clearance and iothalamate-derived GFR determinations.Results. Concentration-dependent renal clearance of PAH was observed at plasma concentrations >100 mg/L; renal clearances were 442 +/- 131 (mean +/- SD), 423 +/- 94, 233 +/- 45, and 152 +/- 18 mL/min/1.73 m(2) at plasma concentrations of 18 +/- 2, 92 +/- 5, 291 +/- 47 and 789 +/- 28 mg/L, respectively. The apparent affinity (K-m) and maximum secretory capacity (Tm-PAH) were 141 +/- 70 mg/L and 71 +/- 16 mg/min/1.73 m(2), respectively. The unbound renal clearance and tubular secretory clearance of famotidine were 384 +/- 70 and 329 +/- 78 mL/min/1.73 m(2), respectively, and were not significantly correlated with the unbound plasma concentrations, which ranged from 126 to 2659 ng/mL. The rate of tubular secretion was linear at unbound plasma concentrations up to 2659 ng/mL.Conclusions. These data indicate that a sequential infusion method using PAH may be used to characterize the anionic secretory component of proximal tubular function. The tubular clearance of famotidine may be a suitable index of the cationic secretory capacity of the proximal tubule in humans. Saturation of the cationic secretory pathway was not observed, and further investigation into parallel pathways of cationic secretion, such as p-glycoprotein, may be warranted.