García-Mayor R V, Pérez A J, Gandara A, Andrade A, Mallo F, Casanueva F F
Endocrine Section, Hospital General, Vigo, Spain.
Clin Endocrinol (Oxf). 1993 Sep;39(3):337-43. doi: 10.1111/j.1365-2265.1993.tb02374.x.
Several disturbances in the regulation of growth hormone secretion have been reported in chronic renal failure. The general assumption is that an altered hormonal clearance is at the basis of such GH alterations. Nevertheless, details of GH elimination kinetics in uraemia are not available. To clarify the role played by the kidney in its catabolism, GH elimination kinetics were studied in uraemic and control subjects after suppression of endogenous secretion of GH.
In all subjects an analogue of somatostatin (octreotide 100 micrograms i.v.) was administered as a bolus before GH (-60 minutes). Sixty minutes later (0 min) biosynthetic GH (0.5 IU = 200 micrograms) was administered intravenously as a bolus.
Six chronic renal failure patients before dialysis and six matched normal volunteers.
Plasma GH levels were measured by an immunoradiometric assay.
In both groups, the GH elimination curve fitted a bi-exponential model. The calculated plasma volume and GH concentration at 0 minutes were similar in both groups, while uraemic patients presented a reduced distribution volume. In all parameters measuring GH elimination, chronic renal failure patients showed an impaired clearance. In fact, the area under the curve (mU/l/150 min) was 912.8 +/- 170.6 for controls and 3524.8 +/- 642.8 for chronic renal failure patients (P < 0.005). The GH half-life was 13.8 +/- 1.6 and 26.4 +/- 2.9 minutes for control and uraemic subjects respectively (P < 0.05), and the metabolic clearance rate MCR (ml/min/m2) was 265.3 +/- 50.6 for controls and 79.9 +/- 16.4 for uraemic patients (P < 0.05). The GH mean residence time (minutes) (MRT) calculated was 12.0 +/- 0.5 for controls and 31.8 +/- 4.6 for chronic renal failure patients (P < 0.05).
Contrary to previous estimates, GH elimination kinetics follows a bi-exponential model and in normal subjects the GH half-life of the second phase is 13.8 +/- 1.6 minutes. Uraemic patients have impaired clearance of GH, suggesting that the kidney plays a role in GH disposal. However, the degree of impairment does not fully explain the alterations in GH secretion previously described in chronic renal failure.
慢性肾衰竭患者生长激素分泌调节存在多种紊乱情况。一般认为激素清除改变是生长激素变化的基础。然而，尿毒症患者生长激素清除动力学的细节尚不清楚。为阐明肾脏在其分解代谢中的作用，在抑制内源性生长激素分泌后，对尿毒症患者和对照受试者的生长激素清除动力学进行了研究。
在所有受试者中，于生长激素给药前60分钟静脉推注100微克生长抑素类似物（奥曲肽）。60分钟后（0分钟）静脉推注生物合成生长激素（0.5国际单位 = 200微克）。
6例透析前慢性肾衰竭患者和6例匹配的正常志愿者。
采用免疫放射分析法测量血浆生长激素水平。
两组的生长激素清除曲线均符合双指数模型。两组0分钟时计算的血浆容量和生长激素浓度相似，而尿毒症患者的分布容积减小。在所有测量生长激素清除的参数中，慢性肾衰竭患者的清除率受损。实际上，对照组曲线下面积（毫单位/升/150分钟）为912.8±170.6，慢性肾衰竭患者为3524.8±642.8（P<0.005）。对照组和尿毒症受试者的生长激素半衰期分别为13.8±1.6分钟和26.4±2.9分钟（P<0.05），代谢清除率（MCR，毫升/分钟/平方米）对照组为265.3±50.6，尿毒症患者为79.9±16.4（P<0.05）。计算得出的生长激素平均驻留时间（分钟）对照组为12.0±0.5，慢性肾衰竭患者为31.8±4.6（P<0.05）。
与先前估计相反，生长激素清除动力学符合双指数模型，正常受试者第二阶段的生长激素半衰期为13.8±1.6分钟。尿毒症患者生长激素清除受损，提示肾脏在生长激素清除中起作用。然而，受损程度并不能完全解释先前描述的慢性肾衰竭患者生长激素分泌的改变。
