McConnell R F, Lorentz W B, Berger M, Smith E H, Carvajal H F, Travis L B
Pediatr Res. 1977 Jan;11(1 Pt 1):33-6.
The authors have evaluated urinary adenosine 3',5'-monophosphate (cyclic AMP) excretion and renal function during Pitressin administration, hypertonic saline administration, and water deprivation in two siblings with vasopressin-resistant diabetes insipidus and in normal control subjects. After vasopressin administration normal subjects experienced a 2-fold rise in urinary cyclic AMP excretion from 3.2 +/- 0.7 to 5.6 +/- 1.3 nmol/min (P less than 0.001) whereas cyclic AMP excretion was unchanged in both patients (patient AC 4.4 +/- 0.9 to 4.3 +/- 2.1; patient TC 2.2 +/- 0.9 to 2.6 +/- 0.9 nmol/min) with nephrogenic diabetes insipidus (NDI). Urinary cyclic AMP excretion was measured during infusion of 2.5% saline, after vasopressim administration, and after water deprivation. Cyclic AMP excretion was not different from control values in the NDI patients during any of the experimental conditions. Furthermore, there was no difference in cyclic AMP excretion when periods of dilute urine excretion (patient AC 4.5 +/- 1.1; patient TC 2.1 +/- 0.8 nmol/min) were compared with periods when urine concentration was greater than that of plasma (AC 3.5 +/- 1.3; TC 1.8 +/- 0.9 nmol/min). Both subjects responded to parathyroid hormone infusion with a 2-fold increase in urinary cyclic AMP excretion. Excretion of concentrated urine was paralleled by a marked decrease in urine flow to less than 1 ml/min/m2. During periods of hypotonic urine excretion (Uosm/Posm less than 1.0) average glomerular filtration rate (GFR) in patient AC was 67.0 +/- 3.0 ml/minm2 whereas in patient TC it was 70.1 +/- 8.1 ml/min/m2. When each patient was excreting a hypertonic urine (Uosm/Posm greater than 1.0) after fluid deprivation their GFR had decreased significantly (P = 0.001) to 31.6 +/- 8.9 and 33.3 +/- 10.3 ml/min/m2, respectively. Ability of these two subjects with NDI to concentrate their urine to Uosm/Posm greater than 1.0 in the absence of an increase in urinary cyclic AMP but associated with a decrease in GFR to 50% normal indicates that urinary concentration was effected by a reduction in GFR rather than a partial response to antidiuretic hormone (ADH). Their ability to concentrate their urine during periods of modest volume depletion would protect them from progressing to more severe stages of dehydration and result in the relatively benign course of their disease. It is feasible that in patients previously reported to have had clinically "partial" NDI this mechanism may have been operative.
作者评估了两名患有抗血管加压素性尿崩症的同胞以及正常对照者在使用垂体后叶素、输注高渗盐水和禁水期间的尿3',5'-单磷酸腺苷（环磷酸腺苷）排泄及肾功能。给予血管加压素后，正常受试者尿环磷酸腺苷排泄量从3.2±0.7 nmol/分钟增至5.6±1.3 nmol/分钟，升高了2倍（P<0.001），而两名患有肾性尿崩症（NDI）的患者（患者AC从4.4±0.9至4.3±2.1；患者TC从2.2±0.9至2.6±0.9 nmol/分钟）的环磷酸腺苷排泄量未发生变化。在输注2.5%盐水期间、给予血管加压素后以及禁水后测量尿环磷酸腺苷排泄量。在任何实验条件下，NDI患者的环磷酸腺苷排泄量与对照值均无差异。此外，将尿液稀释期（患者AC为4.5±1.1；患者TC为2.1±0.8 nmol/分钟）与尿渗透压高于血浆渗透压期（AC为3.5±1.3；TC为1.8±0.9 nmol/分钟）相比，环磷酸腺苷排泄量也无差异。两名受试者对甲状旁腺激素输注的反应均为尿环磷酸腺苷排泄量增加2倍。尿液浓缩时，尿流量显著减少至低于1 ml/分钟/平方米。在低渗性尿排泄期（尿渗透压/血浆渗透压<1.0），患者AC的平均肾小球滤过率（GFR）为67.0±3.0 ml/分钟/平方米，而患者TC为70.1±8.1 ml/分钟/平方米。当每位患者在禁水后排出高渗尿（尿渗透压/血浆渗透压>1.0）时，其GFR显著降低（P = 0.001），分别降至31.6±8.9和33.3±10.3 ml/分钟/平方米。这两名NDI受试者在尿环磷酸腺苷不增加但GFR降至正常的50%的情况下，能够将尿液浓缩至尿渗透压/血浆渗透压>1.0，这表明尿液浓缩是由GFR降低所致，而非对抗利尿激素（ADH）的部分反应。他们在轻度容量耗竭期间浓缩尿液的能力可保护他们不发展至更严重的脱水阶段，并导致其疾病病程相对良性。先前报道临床上患有“部分性”NDI的患者可能存在这种机制，这是可行的。
