Abstract
Supraphysiological doses of rhGH are used for treatment of renal growth failure. Because of reduced renal MCR of rhGH this may result in accumulation of rhGH. To determine the quanlity of renal and extrarenal MCR of rhGH in chronic renal failure (CRF) we performed stepwise steady-state infusion studies of rhGH in 12 patients (pts) with CRF (6 adults, 6 children; GFR range 8 to 44 ml/min × 1.73 m2) and 24 healthy adult controls (Co). Endogenous GH secretion was suppressed by i.v. infusion of octreoude (2 ug/1.73 m2 × h). HGH was infused at three different rates, resulting in mean plasma levels of 5 (I), 30 (II) and 57 (III) ug/l. GFR was measured by simultaneous inulin clearance. Plasma and urin hGH concentrations were measured by monoclonal IRMA. - MCR of rhGH was significantly reduced in pts compared to Co at each infusion rate (I: 139 ± 65 vs 207 ± 61, p < .01; II: 76 ±35 vs 124 ± 22, p< .001; III: 58± 15 vs 113 ± 17, p < .001 ml/min × m2). In both pts and Co MCR decreased significantly with increasing GH plasma concentrations (p < .01). MCR was correlated to GFR (r = 0.86, p< .001). Calculated extrarenal MCR did not differ between pts and Co at any given GH plasma concentration. T 1/2 was significantly prolonged in pts compared to Co (I: 22 ± 9 vs 13 ± 4, p < .01; II: 27 ± 6 vs 18 ± 5, p< .001; III: 30 ± 6 vs 21 ± 4, p < .001 min). In Co urinary GH excretion was dose dependent but minimal and urinary excretion fraction (0.1 × 10−4) remained constant.
Conclusions: (I) In Co renal MCR and rhGH amounts 10 about 50 % of total MCR. (II) Renal and total MCR is correlated to GFR. (III) Extrarenal MCR does not increase if renal MCR is low. (IV) In Co and pts MCR is inversely correlated to GH plasma concentration, pointing to extrarenal saturation mechanisms. (V) Adjustment of rhGH doses to GFR should be considered in CRF.
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Haffner, D., Schaefer, F., Girard, J. et al. GLOMERULAR FILTRATION RATE (GFR) DETERMINES METABOLIC CLEARANCE RATE (MCR) OF HGH. Pediatr Res 33 (Suppl 5), S63 (1993). https://doi.org/10.1203/00006450-199305001-00361
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DOI: https://doi.org/10.1203/00006450-199305001-00361