Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans

• Published in: Metabolism, clinical and experimental Vol. 48; no. 6; pp. 763 - 770
• Main Authors: Mahlbacher, Katia, Sicuro, Anita, Gerber, Hans, Hulter, Henry N., Krapf, Reto
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.1999; Elsevier
• Subjects: Acidosis, Renal Tubular - blood; Acidosis, Renal Tubular - metabolism; Acidosis, Renal Tubular - urine; Biological and medical sciences; Calcium - metabolism; Case-Control Studies; Female; Growth Hormone - administration & dosage; Growth Hormone - metabolism; Humans; Kidney - metabolism; Magnesium - blood; Magnesium - metabolism; Magnesium - urine; Male; Medical sciences; Metabolic diseases; Nitrogen - blood; Nitrogen - metabolism; Nitrogen - urine; Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...); Phosphates - blood; Phosphates - metabolism; Phosphates - urine; Volunteers; Human; Phosphates; Renal function; Somatotropin hormone; Hypoproteinemia; Acid base balance disorder; Biological activity; Protein hormone; Metabolic disorder; Depletion; Adenohypophyseal hormone; Nitrogen balance; Metabolic acidosis
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(99)90177-4

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (Δ[HCO 3], −10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH 4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 ± 1.4 to 87 ± 8.4 nmol/L (control level, 36.4 ± 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH) 2D) and further decreased intact PTH (from 10 ± 1 to 6 ± 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH) 2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO 4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.