Are insulin-like growth factor and its binding proteins 1 and 3 clinically useful as markers of malnutrition, sarcopenia and inflammation in end-stage renal disease?
BACKGROUND
Malnutrition is common in end-stage renal disease (ESRD) and affects both morbidity and mortality. The growth hormone-dependent insulin-like growth factor (IGF)-I may be a good marker of malnutrition because of its short half-life. In the present study, we investigate the influence of decreasing residual renal function as well as of chronic inflammation on the IGF system to assess its usefulness in this patient group.


METHODS
Cross-sectional analysis of 220 ESRD patients (140 males) with a mean age of 52+/-1 years. Biochemical analyses of insulin, IGF-I, IGFBP-1, IGFBP-3, IL-6, high sensitivity (hs)-CRP and other routine markers. Malnutrition status was recorded using subjective global assessment (SGA), body mass index, estimated protein intake from nitrogen appearance (nPNA), handgrip strength (HGS) and insulin resistance (HOMA-IR). Dual energy X-ray absorptiometry was used to assess body composition.


RESULTS
Both IGF-I and IGFBP-1 showed significant and opposite correlations with most markers of nutritional status, including SGA (rho=-0.29 and 0.27; P<0.001), nPNA (rho=0.18 and -0.22; P<0.05), S-creatinine (rho=0.19 and -0.19; P<0.01) and HGS (rho=0.21 and -0.25; P<0.01). IFG-I was strongly correlated with IGFBP-3 (rho=0.62; P<0.001) and inversely correlated with IGFBP-1 (rho=0.44; P<0.001). Both IGF-I and IGFBP-3, but not IGFBP-1, were significantly correlated with age (rho=-0.25 for IGF-I and -0.35 for IGFBP-3; P<0.001) and hsCRP (rho=-0.21 and -0.32; P<0.01). In multivariate analysis, SGA and s-albumin were independent predictors of both IGF-I and IGFBP-1.


CONCLUSIONS
Both IGF-I and IGFBP-1 appear to correlate well with markers of protein-energy malnutrition and sarcopenia. However, IGF-I is also influenced by age, whereas IGFBP-1 is influenced by glucose metabolism. IGFBP-3 does not correlate with nutritional status in ESRD, perhaps because of a strong association with inflammation.
Axelsson
J
J
1ivisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden. jonas.axelsson@klinvet.ki.se
Qureshi
A R
AR
Divino-Filho
J C
JC
Bárány
P
P
Heimbürger
O
O
Lindholm
B
B
Stenvinkel
P
P
D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D018737:Hand Strength; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D015850:Interleukin-6; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000175:diagnosis; D008875:Middle Aged; D015999:Multivariate Analysis; D009133:Muscular Atrophy / Q000097:blood / Q000175:diagnosis; D015596:Nutrition Assessment; D009748:Nutrition Disorders / Q000175:diagnosis / Q000209:etiology; D009752:Nutritional Status; D011237:Predictive Value of Tests; D013002:Somatomedins / Q000378:metabolism*
D015415:Biomarkers; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D013002:Somatomedins; D002097:C-Reactive Protein