PURPOSE: The purpose of the study was to find if IGF-1 and IGFBP-3 levels were altered with varied kidney function in a large sample of the U.S. population. Then, to exam whether IGF-1 and IGFBP-3 levels were altered with varied protein intake in all levels of kidney function.
METHODS: Participants included a subsample of 6058 participants from the National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), a nationally representative sample of apparently healthy, non-institutionalized participants ages > 20 years. Statistical analysis was conducted utilizing Statistical Analysis Systems (SAS, version 9.1, Cary, NC) and SUDDAN (Release 5.50, Research Triangle Park, NC) to account for the complex survey sampling. General differences in IGF protein concentrations across subjects categorized by demographic and body mass index (BMI) categories were investigated. Analysis of variance (ANOVA) for continuous variables and Wald’s Chi Square test for categorical data were utilized to compare IGF protein concentrations across classification groups. Kidney function was assessed using the simplified Modification of Diet in Renal Disease (MDRD) formula with standardized serum creatinine to estimate glomerular filtration rate (GFR). Multiple backwards stepwise regressions were employed to test the effects of multiple variables in predicting IGF protein concentrations and kidney function.
RESULTS: Age and sex were significant covariates for IGF-1, IGFBP-3 concentrations, and IGF-1/IGFBP-3 molar ratio. IGF-I concentrations were related to race/ethnicity with the lowest concentrations observed in Mexicans Americans. There was an inverse relationship observed between IGF-I and IGFBP-3 and body mass index. IGF-I/IGFBP-3 concentrations were significantly lower in participants with diabetes compared to those with normal blood glucose concentrations. Participants with hypertension had significantly lower IGF protein concentrations. Forty-two percent of the population had mild kidney failure (GFR 60-89 ml/min) and 4.5% displayed moderate to severe kidney failure (GFR <60 ml/min). Age-adjusted IGF-1, IGFBP-3, and IGF-1/IGFBP-3 increased significantly with declining kidney function. Total dietary protein intake was positively correlated with serum IGF-1 concentrations in participants with mild or moderate to severe kidney failure. Total protein intake was greater in participants with normal kidney function compared to those with decreased kidney function. Animal protein intake was more strongly correlated with IGF-1 concentrations than vegetable protein intake in participants with normal or decreased kidney function, however, the correlation was weak. Multiple regression models including age, sex, race/ethnicity, GFR, BMI, fasting plasma glucose, total, animal and vegetable protein intakes, and total dietary fat intake explained 29% of the variability in serum IGF-I. Kidney function (GFR) was predicted by age, race/ethnicity, IGF-I, diastolic blood pressure, fasting plasma glucose and dietary kcalories/kg intake (R2 = 0.3182).
CONCLUSION: IGF proteins are important anabolic growth factors that are influenced by nutritional status, growth hormone, and general metabolic and disease status. In the present large cross-sectional study of U.S. adults, IGF-I and IGFBP-3 protein concentrations were statistically related to age, sex, obesity, diabetes, hypertension, dietary intake, and kidney function. Age-adjusted IGF-1, IGFBP-3, and the molar ratio of IGF-1/IGFBP-3 all increased with declining kidney function. Protein intake was lower in participants with impaired kidney function and was weakly correlated with IGF-I concentrations, however, strong differences between vegetable versus animal protein intake were not apparent. Thus serum IGF proteins, particularly IGF-I, were useful in predicting kidney failure in a population with widely varying kidney function. Additional studies are needed, however, serum IGF-I concentrations may be a useful marker of overall kidney function as well as a marker of nutritional status in kidney failure.