Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome
Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome
复制标题
DOI：
10.1681/asn.v1161100
复制
发表时间：
2000-06-01
影响因子：
13.6
通讯作者：
Brater, DC
中科院分区：
文献类型：
--
作者：
Agarwal, R;Gorski, JC;Brater, DC
肾病综合征(NS)患者对环状利尿剂的反应低于正常。在NS动物模型上的研究表明，利尿剂与尿白蛋白的结合可能是利尿剂抵抗的机制之一。为了探索这一假设，对12名NS患者进行了研究，以确定与磺胺恶唑结合的尿蛋白置换是否能恢复对120 mg速尿的反应。这项研究在治疗了七名患者后停止，因为很明显磺胺恶唑没有效果。单用速尿的钠排泄量(平均+/-SD)为239+/-90，磺胺唑组为240+/-115mEq/8h。磺胺恶唑对速尿的血药动力学影响不大，但对速尿的尿排出时程和总排泄量均无影响：单用速尿49+/-15 mg，速尿+磺胺恶唑54+/-12 mg。结论：尿蛋白结合环状利尿剂不是NS利尿剂抵抗的主要机制。反过来，旨在取代这种束缚的策略不太可能在临床上有所帮助。
Response to loop diuretics in patients with nephrotic syndrome (NS) is subnormal. Studies in animal models of NS have suggested that binding of diuretic to urinary albumin is one of the mechanisms that may be operative in this diuretic resistance. To explore this hypothesis, 12 patients with NS were studied to determine whether displacement from urinary protein binding with sulfisoxazole would restore response to 120 mg of furosemide. The study was stopped after treating seven patients because it was clear that sulfisoxazole had no effect. Sodium excretion (mean +/- SD) from furosemide alone was 239 +/- 90 versus 240 +/- 115 mEq/8 h with sulfisoxazole. Sulfisoxazole had modest effects on serum pharmacokinetics of furosemide but had no effect on either the time course of furosemide urinary excretion or overall amount excreted: 49 +/- 15 mg versus 54 +/- 12 mg for furosemide alone and furosemide plus sulfisoxazole, respectively. It is concluded that urinary protein binding of loop diuretics is not a major mechanism for the diuretic resistance of NS. In turn, strategies aimed at displacing such binding are unlikely to be clinically helpful.