A PATHOPHYSIOLOGICAL INTERPRETATION OF UNRESPONSIVENESS TO SPIRONOLACTONE IN A STEPPED-CARE APPROACH TO THE DIURETIC TREATMENT OF ASCITES IN NONAZOTEMIC CIRRHOTIC-PATIENTS
A PATHOPHYSIOLOGICAL INTERPRETATION OF UNRESPONSIVENESS TO SPIRONOLACTONE IN A STEPPED-CARE APPROACH TO THE DIURETIC TREATMENT OF ASCITES IN NONAZOTEMIC CIRRHOTIC-PATIENTS
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DOI：
10.1002/hep.1840140205
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发表时间：
1991-08-01
期刊：
影响因子：
13.5
通讯作者：
MERKEL, C
中科院分区：
文献类型：
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作者：
GATTA, A;ANGELI, P;MERKEL, C
有人推测近端钠重吸收的程度影响非氮质血症性腹水患者对醛固酮拮抗剂的反应。 为了验证这一假设，我们评估了肾内钠处理锂清除率在51名非氮血症腹水型糖尿病患者和23名对照谁保持相同的低钠饮食（80 mmol/天）。 51例尿毒症患者中有7例进行了自发性利尿，而44例需要利尿剂治疗。 治疗开始时使用螺内酯，剂量为150 mg，每日一次。 剂量增加至300 mg，如果随后无反应，则增加至500 mg，每日一次。 使用500 mg安体舒通后未出现腹水动员的肝硬化患者随后接受联合利尿方案治疗，包括固定剂量的安体舒通（500 mg每日一次）和初始剂量为50 mg每日一次的呋塞米。 如果未观察到反应，则将剂量增加至100、150和200 mg，每日一次。 对利尿剂治疗的反应定义为每3天体重减轻大于700 gm，直至临床上检测不到腹水。 对螺内酯无反应者（43%）显示较低的钠排泄分数（0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p < 0.001），这是因为向远端小管的钠递送分数（18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p < 0.025）低于反应者。 此外，无应答者显示远端钠重吸收率较低，无论是绝对值（2，360 +/- 723-mu-Eq/min vs. 3，221 +/- 960-mu-Eq/min; p < 0.01）和占滤过钠负荷的百分比（17.5% +/- 5.7% vs. 23.1% +/- 7.6%; p < 0.01），尽管血浆醛固酮值较高（524 +/- 542 pg/ml vs. 136 +/- 213 pg/ml; 025）我们的结论是，非氮质血症性腹水患者对足够剂量的螺内酯无反应与病理生理条件有关，其中醛固酮在肾功能中的作用，钠潴留受到显著增强的近端钠重吸收的限制。
It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p < 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p < 0.025) than responders. Moreover, nonresponders showed lower distal sodium reabsorption, both in absolute terms (2,360 +/- 723-mu-Eq/min vs. 3,221 +/- 960-mu-Eq/min; p < 0.01) and as a percentage of filtered sodium load (17.5% +/- 5.7% vs. 23.1% +/- 7.6%; p < 0.01) despite higher values of plasma aldosterone (524 +/- 542 pg/ml vs. 136 +/- 213 pg/ml; p < 0.025).We conclude that unresponsiveness to adequate doses of spironolactone in nonazotemic ascitic cirrhotic patients is related to a pathophysiological condition in which the role of aldosterone in renal sodium retention is limited by markedly enhanced proximal sodium reabsorption.