Saito T, Ishikawa S E, Ando F, Okada N, Nakamura T, Kusaka I, Higashiyama M, Nagasaka S, Saito T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
J Clin Endocrinol Metab. 1998 Nov;83(11):4034-40. doi: 10.1210/jcem.83.11.5218.
The present study was undertaken to determine whether urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose the pathological state of water retention and hyponatremia. UAQP-2 under ad libitum water drinking was 429 fmol/mg creatinine in the patients with water retention, a value significantly greater than that of 153 fmol/mg creatinine in the normal subjects. An acute oral water load test (20 mL/kg BW) was performed in 7 normal subjects (22-25 yr old) and 10 patients with water retention and hyponatremia (55-75 yr old). The percent excretion of the water load was only 30% in the patient group compared with 70% in the control group (P < 0.01). In the control group, minimal urinary osmolality was as low as 131 mosmol/kg H2O, which was responsible for the decrease in plasma arginine vasopressin (AVP) levels after the reduction in plasma osmolality. In the patient group, minimal urinary osmolality was 320 mosmol/kg H2O, and free water clearance remained below 0.6 mL/min after the water load. This impaired water excretion was consistent with the nonsuppressible levels of plasma AVP despite hypoosmolality. The nadir of UAQP-2 was obtained at 60-90 min. The minimal UAQP-2 was reduced to 284 fmol/mg creatinine, a value significantly greater than that of 76 fmol/mg creatinine in the control group. Similar results were obtained in the 6 patients with hypopituitarism, who had impaired water excretion and marked hyponatremia. Water excretion was totally normalized after the replacement of hydrocortisone (excretion of water load, 31% vs. 102%; P < 0.01). Hydrocortisone replacement also significantly reduced the minimal UAQP-2 from 225 to 49 fmol/mg creatinine after the acute oral water load, a value comparable to that in the control subjects. These results indicate that UAQP-2 is a potent marker to diagnose the pathological state of impaired water excretion and hyponatremia, dependent upon AVP, in patients with water retention and hypopituitarism.
本研究旨在确定水通道蛋白-2（UAQP-2）的尿排泄量对诊断水潴留和低钠血症的病理状态是否有价值。水潴留患者自由饮水时UAQP-2为429 fmol/mg肌酐，该值显著高于正常受试者的153 fmol/mg肌酐。对7名正常受试者（22 - 25岁）和10名水潴留及低钠血症患者（55 - 75岁）进行了急性口服水负荷试验（20 mL/kg体重）。患者组水负荷的排泄率仅为30%，而对照组为70%（P < 0.01）。在对照组中，最低尿渗透压低至131 mosmol/kg H₂O，这导致血浆渗透压降低后血浆精氨酸加压素（AVP）水平下降。在患者组中，最低尿渗透压为320 mosmol/kg H₂O，水负荷后自由水清除率仍低于0.6 mL/min。尽管存在低渗状态，但这种水排泄受损与血浆AVP不可抑制的水平一致。UAQP-2的最低点在60 - 90分钟时出现。最低UAQP-2降至284 fmol/mg肌酐，该值显著高于对照组的76 fmol/mg肌酐。在6名患有垂体功能减退且水排泄受损和明显低钠血症的患者中也获得了类似结果。补充氢化可的松后水排泄完全恢复正常（水负荷排泄率，31%对102%；P < 0.01）。急性口服水负荷后，氢化可的松替代治疗还使最低UAQP-2从225显著降至49 fmol/mg肌酐，该值与对照组相当。这些结果表明，UAQP-2是诊断水潴留和垂体功能减退患者中依赖AVP的水排泄受损和低钠血症病理状态的有效标志物。
