New insights into diuretic use in patients with chronic renal disease
New insights into diuretic use in patients with chronic renal disease
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DOI：
10.1681/asn.v133798
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发表时间：
2002-03-01
影响因子：
13.6
通讯作者：
Wilcox, CS
中科院分区：
文献类型：
--
作者：
Wilcox, CS
慢性肾功能不全（CRI）或肾病综合征患者经常表现出利尿剂抵抗。CRI患者利尿反应性的限制因素可能包括钠离子重吸收分数的基础水平降低，这对利尿反应产生了上限，下游节段的NaCl重吸收增强，以及向肾脏输送的利尿剂减少。利尿剂是由最近鉴定的有机阴离子转运蛋白（OAT）分泌的，其在近端小管细胞中表达。分泌可能受到残留有机阴离子、尿酸盐或酸中毒的抑制。这些限制需要增加利尿剂的剂量，达到规定的上限水平，并考虑使用非肾代谢的袢利尿剂而不是呋塞米。肾病综合征患者的利尿反应性受到终末肾单位对Na+重吸收的限制。实验研究表明，血清白蛋白浓度降低可增加袢利尿剂的分布容积，减少其肾小管分泌，并通过葡萄糖醛酸化增强呋塞米在肾脏内的失活。袢利尿剂的结合可减少其在Henle袢中的作用。最近的临床研究已经挑战了在动物模型中确定的这些机制中的一些的重要性。改善袢利尿剂反应性的策略包括增加利尿剂剂量，同时使用噻嗪类利尿剂抑制下游NaCl重吸收，并尝试最大限度地减少白蛋白排泄。限制白蛋白排泄的策略包括使用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂以及适当限制蛋白质摄入。这些措施比输注白蛋白溶液更合理、更有效、更便宜。
Patients with chronic renal insufficiency (CRI) or the nephrotic syndrome frequently manifest diuretic resistance. Factors limiting diuretic responsiveness in patients with CRI may include a reduced basal level of fractional Na+ reabsorption that places an upper limit on diuretic response, and enhanced NaCl reabsorption in downstream segments, combined with a reduced delivery of diuretic to the kidney. Diuretics are secreted by the recently characterized organic anion transporters (OATs), which are expressed in proximal tubule cells. Secretion may be inhibited by retained organic anions, urate, or acidosis. These limitations necessitate an increased diuretic dosage, up to a defined ceiling level, and consideration of the use of a nonrenally metabolized loop diuretic rather than furosemide. Diuretic responsiveness in patients with the nephrotic syndrome is limited by avid Na+ reabsorption by the terminal nephron. Experimental studies have shown that a reduced serum albumin concentration can increase the volume of distribution of loop diuretics, reduce their tubular secretion, and enhance the inactivation of furosemide within the kidney by glucuronidization. Binding of loop diuretics can curtail their action in the loop of Henle. Recent clinical investigations have challenged the importance of some of these mechanisms that were identified in animal models. Strategies to improve loop diuretic responsiveness include increasing diuretic dosage, concurrent use of a thiazide diuretic to inhibit downstream NaCl reabsorption and attempts to maximally reduce albumin excretion. Strategies to limit albumin excretion include the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and appropriate limitation of protein intake. These measures are more logical, effective, and less expensive than infusion of albumin solutions.