慢性肾脏病患者血清可溶性Fas（sFas）水平升高：肾脏清除、重吸收及合成的影响

High serum levels of soluble Fas (sFas) in CKD patients: effects of renal clearance, reabsorption and synthesis.

作者信息

Dalboni M A, Cenedeze M A, Manfredi S R, Cruz Andreoli M C, Pavao Dos Santos O, Canziani M E, Boim M A, Goes M A, Draibe S A, Balakrishnan V, Cendoroglo M

机构信息

Division of Nephrology, Department of Medicine, Federal University of San Paulo, San Paulo - Brazil.

出版信息

Int J Artif Organs. 2008 May;31(5):405-10. doi: 10.1177/039139880803100505.

DOI:10.1177/039139880803100505

PMID:18609513

Abstract

PURPOSE

Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD.

MATERIALS AND METHODS

We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes.

RESULTS

Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001).

CONCLUSIONS

In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.

摘要

目的

据报道，慢性肾脏病（CKD）患者血清可溶性Fas（sFas）浓度升高。然而，关于sFas的肾脏清除率、sFas是否在肾小管中重吸收或CKD中sFas合成的行为知之甚少。

材料与方法

我们研究了69例CKD患者（年龄60±15岁，肌酐清除率37±19 ml/min/1.73 m²）和14名健康受试者（年龄61±17岁，肌酐清除率79±24 ml/min/1.73 m²）。采用酶联免疫吸附测定（ELISA）法检测sFas水平（pg/mL）和视黄醇结合蛋白（RBP - mg/L）。采用逆转录聚合酶链反应（RT-PCR）定量白细胞sFas mRNA。

结果

CKD患者血清sFas水平显著升高（2781±1214 vs. 2196±773，p = 0.02）。CKD患者24小时尿样中sFas浓度（23±27 vs. 40±17，p = 0.006）和sFas清除率（0.019±0.022 vs. 0.036±0.020，p = 0.01）显著降低。sFas清除率与肌酐清除率相关（r = 0.25，p = 0.02）。尿中RBP浓度与尿中sFas浓度相关（r = 0.80，p < 0.001）。CKD患者sFas mRNA水平较高（3.9±1.8 vs. 2.5±0.9，p < 0.001）。