Knauf H, Mutschler E
Medizinische Klinik I, St. Bernward Krankenhaus, Hildesheim, Germany.
J Cardiovasc Pharmacol. 1997 Mar;29(3):367-72. doi: 10.1097/00005344-199703000-00010.
Diuretic therapy in edematous diseases often yields an inadequate natriuretic response ("diuretic resistance"). To study the functional changes in patients with congestive heart failure, liver cirrhosis with ascites, and nephrotic syndrome, characterized by a reduced effective arterial blood volume (EABV), different diuretic strategies were studied. It was shown that monotherapy with hydrochlorothiazide or furosemide was followed by an inadequate natriuretic response. Correlation of diuretic response with pretreatment fractional sodium excretion of the patient revealed a clear-cut interdependency: Those patients were resistant whose FENa+ was greatly below normal (<0.2%). In addition, it was found that the coadministration of the carboanhydrase inhibitor acetazolamide to diuretic therapy was very effective. We therefore conclude that an increase in proximal-tubular Na+ reabsorption is the major ("pharmacodynamic") determinant for diuretic resistance in edematous diseases with functional "underfilling" of the vascular tree. This alteration of the kidney can easily be overcome by coadministration of a carboanhydrase inhibitor (e.g., acetazolamide).
水肿性疾病的利尿治疗往往产生不充分的利钠反应（“利尿剂抵抗”）。为了研究以有效动脉血容量（EABV）降低为特征的充血性心力衰竭、肝硬化腹水和肾病综合征患者的功能变化，对不同的利尿策略进行了研究。结果表明，单用氢氯噻嗪或呋塞米治疗后利钠反应不充分。利尿剂反应与患者治疗前的钠排泄分数之间的相关性显示出明显的相互依赖性：那些滤过钠排泄分数（FENa+）远低于正常水平（<0.2%）的患者具有利尿剂抵抗。此外，还发现将碳酸酐酶抑制剂乙酰唑胺与利尿治疗联合使用非常有效。因此，我们得出结论，近端小管钠重吸收增加是血管床功能性“充盈不足”的水肿性疾病中利尿剂抵抗的主要（“药效学”）决定因素。通过联合使用碳酸酐酶抑制剂（如乙酰唑胺），肾脏的这种改变很容易被克服。
