Saito T, Fukagawa A, Higashiyama M, Nakamura T, Kusaka I, Nagasaka S, Honda K, Saito T
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi 329-0498 Japan.
J Clin Endocrinol Metab. 2001 Apr;86(4):1665-71. doi: 10.1210/jcem.86.4.7426.
The present study was undertaken to determine whether urinary excretion of aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP) in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old) during the last 5-yr period. Subjects were separated into euvolemic hyponatremia groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with hyponatremia was derived from hypopituitarism, but severe hyponatremia was found in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the elderly. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis in the 3 groups of patients, except for one miscellaneous one. An acute water load test verified the impairment in water excretion, because the percent excretion of the water load was less than 42% and the minimal urinary osmolality was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2 were not reduced after the water load. The inappropriate secretion of AVP was evident in the patients with SIADH and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP-2 and renal water excretion in those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to compensate loss of body fluid in the patients with mineralocorticoid-responsive hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean). Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects.
本研究旨在确定水通道蛋白-2（AQP-2）的尿排泄是否参与了精氨酸加压素（AVP）在过去5年中对33例老年受试者（≥65岁）血钠浓度低于130 mmol/L的低钠血症的影响。受试者被分为等容性低钠血症组：13例垂体功能减退，8例抗利尿激素分泌不当综合征（SIADH），8例老年盐皮质激素反应性低钠血症，4例患有其他杂病。低钠血症患者中约40%源于垂体功能减退，但SIADH和老年盐皮质激素反应性低钠血症患者中发现了严重低钠血症。尽管低渗，但3组患者（除1例杂病患者外）的血浆AVP水平仍相对较高，且与AQP-2尿排泄增加和抗利尿作用密切相关。急性水负荷试验证实了水排泄受损，因为水负荷排泄百分比低于42%，且尿渗透压最低值未充分稀释。此外，水负荷后血浆AVP和AQP-2的尿排泄并未降低。SIADH和垂体功能减退患者中AVP分泌不当明显，氢化可的松替代治疗使垂体功能减退患者的AQP-2尿排泄和肾脏水排泄恢复正常。相比之下，老年盐皮质激素反应性低钠血症患者中适当的抗利尿作用似乎补偿了体液流失，这些患者循环血容量平均减少了7.3%。醋酸氟氢可的松增加了肾脏对钠的处理和体液量，导致老年盐皮质激素反应性低钠血症患者的AVP释放减少和AQP-2尿排泄减少。这些发现表明，与血浆AVP水平相比，AQP-2的尿排泄可能是AVP对肾集合管细胞作用更敏感的指标，并且AQP-2尿排泄增加表明老年低钠血症患者中AVP诱导的抗利尿作用增强。此外，老年盐皮质激素反应性低钠血症必须与老年SIADH仔细鉴别。
