Tramonti Gianfranco, Ferdeghini Marco, Annichiarico Carmela, Donadio Carlo, Norpoth Maria, Mantuano Emanuela, Bianchi Claudio
Department of Internal Medicine, Nephrology Unit, University of Pisa, Pisa, Italy.
J Nephrol. 2003 Sep-Oct;16(5):663-72.
Low molecular weight (LMW) proteins have been proposed for renal function assessment. This study aimed to ascertain the usefulness of tumor-associated trypsin inhibitor (TATI), a LMW protein (6.200 d), as a glomerular filtration rate (GFR) marker. The results were compared with those of beta2-microglobulin and of creatinine (Cr).
Renal handling of TATI labelled with 125I was first studied in rats. Then, in 198 patients, serum TATI levels and GFR (99mTc-DTPA clearance, bladder cumulative method) were determined. To evaluate urine excretion, the fractional TATI clearance was determined in 63 patients.
In rats, total body scan showed a large amount of radioactivity in the kidneys, but not in other organs. The duration of radioactivity demonstrated a peak-time of 11 min. In human beings, the relationship between TATI and GFR was similar to that of beta2-microglobulin and Cr. The increase in TATI with declining renal function was statistically significant, vs. patients with GFR > 100 mL/min, already in the group with GFR 80-100 mL/min (p < 0.05, Bonferroni-Dunn test). The beta2-microglobulin increase was significant in the group with GFR 60-80 mL/min and of Cr in the group with GFR 40-60 mL/min. In patients with renal failure (GFR < 20 mL/min) TATI increased, vs. patients with GFR > 100 mL/min, 13x, beta2-microglobulin 8x and Cr 5x. Urinary excretion of TATI, expressed as fractional clearance, was very low increasing when GFR fell < 40 mL/min.
The kidney plays an important role in the handling of TATI. When GFR fell, the increase in blood levels of TATI was sooner and higher than that of beta2-microglobulin and CR. Consequently, TATI can be added to the group of renal function markers.
低分子量(LMW)蛋白质已被用于评估肾功能。本研究旨在确定肿瘤相关胰蛋白酶抑制剂(TATI)这种低分子量蛋白质(6200道尔顿)作为肾小球滤过率(GFR)标志物的实用性。将结果与β2-微球蛋白和肌酐(Cr)的结果进行比较。
首先在大鼠中研究用125I标记的TATI的肾脏处理情况。然后,测定了198例患者的血清TATI水平和GFR(99mTc-DTPA清除率,膀胱累积法)。为评估尿液排泄情况,在63例患者中测定了TATI的分数清除率。
在大鼠中,全身扫描显示肾脏中有大量放射性,但其他器官中没有。放射性持续时间显示峰值时间为11分钟。在人类中,TATI与GFR的关系与β2-微球蛋白和Cr相似。与GFR>100 mL/min的患者相比,肾功能下降时TATI的升高具有统计学意义,在GFR为80-100 mL/min的组中就已经如此(p<0.05,Bonferroni-Dunn检验)。β2-微球蛋白在GFR为60-80 mL/min的组中升高显著,Cr在GFR为40-60 mL/min的组中升高显著。在肾衰竭患者(GFR<20 mL/min)中,与GFR>100 mL/min的患者相比,TATI升高了13倍,β2-微球蛋白升高了8倍,Cr升高了5倍。以分数清除率表示的TATI尿排泄量非常低,当GFR降至<40 mL/min时增加。
肾脏在TATI的处理中起重要作用。当GFR下降时,TATI血液水平的升高比β2-微球蛋白和Cr更快、更高。因此,TATI可被添加到肾功能标志物组中。