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 end-stage renal disease, for instance intractable malnutrition. The present study was undertaken to establish the therapeutic effect of recombinant human growth hormone (r-hGH) on the nutritional 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 uremic patients on hemodialysis. Thirty hemodialysis patients (13 females and 17 males, mean age 56.7 +/- 15.2 years) were studied who were suffering from malnutrition and could not be treated by any of the usual nutritional therapies; they were subjected to 0.5 IU/kg/week of r-hGH subcutaneously after hemodialysis for 2 weeks. Blood samples were collected for measurement of the following plasma biochemical and hematological indices: serum IGF-I, IGFBP-1, growth hormone, total protein (TP), prealbumin, transferrin, albumin, serum urea nitrogen (SUN), creatinine, hematocrit, and amino acids. Immediately after r-hGH administration, 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 microM/l (p < 0.05 vs. baseline), and from 2,185 +/- 221 to 2,814 +/- 621 microM/l (p < 0.05), respectively. Serum IGF-I increased markedly from 193 +/- 49 to 321 +/- 81 ng/ml, whereas serum IGFBP-1 decreased from 139 +/- 13 to 81 +/- 19 micrograms/l (p < 0.05). Four weeks after r-hGH administration, serum TP and albumin increased from 5.5 +/- 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 significantly higher in patients with an increase of 0.5 g/dl or more in serum albumin than in other patients with poor response and the control group before r-hGH administration. Patients with marked improvement in serum 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 higher 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 addition, 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.
Shinobe
M
M
Department of Medicine, Tokyo Women's Medical College, Japan.
Sanaka
T
T
Nihei
H
H
Sugino
N
N
D000596:Amino Acids / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009748:Nutrition Disorders / Q000188:drug therapy* / Q000209:etiology; D018529:Nutritional Support; D016133:Polymerase Chain Reaction; D006435:Renal Dialysis; D013997:Time Factors; D014511:Uremia / Q000150:complications* / Q000378:metabolism
D000596:Amino Acids; D004044:Dietary Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone