IGF-I IGFBP-1 AS AN INDEX FOR DISCRIMINATION BETWEEN RESPONDER AND NONRESPONDER TO RECOMBINANT HUMAN GROWTH-HORMONE IN MALNOURISHED UREMIC PATIENTS ON HEMODIALYSIS/

From a clinical aspect, there are still a number of unsolved problems in patients with endstage renal disease, for instance intractable maln utrition. The present study was undertaken to establish the therapeuti c effect of recombinant human growth hormone (r-hGH) on the nutritiona l state and clarify the usefulness of the insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-1 (IGFBP-1) ratio as nutritional indices for prediction of the clinical response in urem ic patients on hemodialysis. Thirty hemodialysis patients(13 females a nd 17 males; mean age 56.7 +/- 15.2 years) were studied who were suffe ring from malnutrition and could not be treated by any of the usual nu tritional therapies; they were subjected to 0.5 IU/kg/week of r-hGH su bcutaneously after hemodialysis for 2 weeks. Flood samples were collec ted for measurement of the following plasma biochemical and hematologi cal indices: serum IGF-I, IGFBP-1, growth hormone, total protein (TP), prealbumin, transferrin, albumin, serum urea nitrogen (SUN), creatini ne, hematocrit, and amino acids. Immediately after r-hGH administratio n, SUN, essential amino acid and nonessential amino acid changed from 67.7 +/- 12.3 to 56.5 +/- 10.5 mg/dl (p < 0.05), from 798 +/- 84 to 1, 115 +/- 208 mu M/l (p < 0.05 vs. baseline), and from 2,185 +/- 221 to 2,814 +/- 621 mu M/l (p < 0.05), respectively. Serum IGF-I increased m arkedly from 193 +/- 49 to 321 +/- 81 ng/ml, whereas serum IGFBP-1 dec reased from 139 +/- 13 to 81 +/- 19 mu g/l (p < 0.05). Four weeks afte r r-hGH administration, serum TP and albumin increased from 5.5 rt +/- 0.2 to 6.0 +/- 0.3 g/dl (p < 0.05) and from 3.2 +/- 0.2 to 3.6 +/- 0. 3 g/dl (p < 0.05), respectively. Serum IGF-I/IGFBP-1 ratio was signifi cantly higher in patients with an increase of 0.5 g/dl or more in seru m albumin than in other patients with poor response and the control gr oup before r-hGH administration. Patients with marked improvement in s erum albumin showed an IGF-I/IGFBP-1 ratio of 2 or less. On the other hand, patients without favorable improvement in serum albumin had a hi gher ratio of 4 or more. We conclude that r-hGH and IGF-I improve the malnutritional state by alleviating hypoproteinemia and abnormality of serum amino acid profile in uremic patients on hemodialysis. In addit ion, the serum IGF-I/IGFBP-1 ratio is useful not only as a nutritional parameter but also as a predicting index of responsiveness to r-hGH.