Metabolic clearance rate of biosynthetic growth hormone after endogenous growth hormone suppression with a somatostatin analogue in chronic renal failure patients and control subjects

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Abstract
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.