title: Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans.
abstract: 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 (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/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 PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.
authors.affiliation: Klinik B für Innere Medizin, Kantonsspital St. Gallen.
authors.forename: K
authors.initials: K
authors.lastname: Mahlbacher
authors.forename: A
authors.initials: A
authors.lastname: Sicuro
authors.forename: H
authors.initials: H
authors.lastname: Gerber
authors.forename: H N
authors.initials: HN
authors.lastname: Hulter
authors.forename: R
authors.initials: R
authors.lastname: Krapf
mesh_terms: D000141:Acidosis, Renal Tubular / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008274:Magnesium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D009584:Nitrogen / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014838:Volunteers
chemical_list: D010710:Phosphates; D013006:Growth Hormone; D008274:Magnesium; D009584:Nitrogen; D002118:Calcium