Rastogi S P, Crawford C, Wheeler R, Flanigan W, Arruda J A
J Lab Clin Med. 1984 Aug;104(2):271-82.
Furosemide stimulates urinary acidification in normal humans probably by increasing distal Na delivery and transport, thus creating a favorable electric gradient for H+ and K secretion. Therefore, furosemide should stimulate urinary acidification in patients with distal renal tubular acidosis, provided the distal nephron is capable of transporting Na and the H+ pumps can respond to the favorable electric gradient. We examined the effect of short-term furosemide administration on urinary acidification in five normal participants and 12 patients with normokalemic, hypokalemic, or hyperkalemic distal renal tubular acidosis. In controls, furosemide decreased urine pH and increased net acid and K excretion. In six of eight patients with normokalemic or hypokalemic renal tubular acidosis, furosemide decreased urine pH and increased net acid and K excretion to levels not significantly different from control values. The patients that had normal responses were interpreted as having a rate-dependent or gradient distal renal tubular acidosis, and thus increased distal Na delivery created a favorable electric gradient for H+ and K secretion. The normokalemic patients who did not have a response were considered to have a defect in the pumps (secretory defect). Of the four hyperkalemic patients, two had a voltage-dependent defect and the other two had aldosterone deficiency. The patients with selective aldosterone deficiency had low baseline urine pH values that did not change with furosemide administration, but net acid and K excretion did increase significantly. The patients with voltage-dependent defect did not lower urine pH or increase net acid and K excretion. Our data demonstrate that administration of furosemide enhances urinary acidification in certain patients with distal renal tubular acidosis. We suggest that furosemide administration may be useful in the characterization of the mechanism responsible for distal renal tubular acidosis and in the treatment of distal renal tubular acidosis in selected patients.
呋塞米可能通过增加远端肾小管钠的递送和转运，从而为氢离子和钾离子的分泌创造有利的电位梯度，来刺激正常人的尿液酸化。因此，只要远端肾单位能够转运钠且氢离子泵能够对有利的电位梯度作出反应，呋塞米就应该能刺激远端肾小管酸中毒患者的尿液酸化。我们研究了短期给予呋塞米对5名正常受试者和12名患有正常血钾、低钾血症或高钾血症的远端肾小管酸中毒患者尿液酸化的影响。在对照组中，呋塞米降低了尿液pH值，并增加了净酸排泄和钾排泄。在8名正常血钾或低钾血症肾小管酸中毒患者中的6名，呋塞米降低了尿液pH值，并增加了净酸排泄和钾排泄，使其水平与对照值无显著差异。有正常反应的患者被认为患有速率依赖性或梯度性远端肾小管酸中毒，因此增加的远端肾小管钠递送为氢离子和钾离子的分泌创造了有利的电位梯度。没有反应的正常血钾患者被认为存在泵功能缺陷（分泌缺陷）。在4名高钾血症患者中，2名存在电压依赖性缺陷，另外2名存在醛固酮缺乏。选择性醛固酮缺乏的患者基线尿液pH值较低，给予呋塞米后未发生变化，但净酸排泄和钾排泄确实显著增加。存在电压依赖性缺陷的患者未降低尿液pH值，也未增加净酸排泄和钾排泄。我们的数据表明，给予呋塞米可增强某些远端肾小管酸中毒患者的尿液酸化。我们建议，给予呋塞米可能有助于明确远端肾小管酸中毒的发病机制，并对部分患者的远端肾小管酸中毒进行治疗。
