IGF-1 and Survival in ESRD

Abstract

SummaryBackground and objectives IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients.Design, setting, participants, & measurements Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models.Results At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50). ConclusionIn incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it predicts increased mortality risk.

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

“…19 To investigate whether immobilization of IGF-1C could enhance therapeutic effects of stem cells, IGF-1C was grafted onto the side chain of CS to obtain CS-IGF-1C ( Figure 1A). Successful IGF-1C coupling to the side group of alkynyl-substituted CS was 21 C≡C stretching) disappeared and lowered. In addition, the peaks at 2831 and 1172 cm 21 were seen as a result of C-H stretching of methylene and methyl groups and C-O stretching of hydroxyl group in the grafted IGF-1C segment ( Figure 1B).…”

“…Successful IGF-1C coupling to the side group of alkynyl-substituted CS was 21 C≡C stretching) disappeared and lowered. In addition, the peaks at 2831 and 1172 cm 21 were seen as a result of C-H stretching of methylene and methyl groups and C-O stretching of hydroxyl group in the grafted IGF-1C segment ( Figure 1B). This finding indicates the immobilization of IGF-1C to the side group of alkynyl-substituted CS.…”

“…47 The FT-IR transmittance spectrum in a wavelength region from 4000 to 500 cm 21 was acquired using an FT-IR spectrometer (FTS-6000 spectrometer; Bio-Rad, Hercules, CA). Rheologic measurement was performed on a 25-mm parallel-plate rheometer (TA Instruments, New Castle, DE).…”

“…19 IGF-1 is a potent mitogenic and prosurvival factor and is implicated as a key mediator in renal recovery in clinical settings. 20,21 The C domain peptide of IGF-1 (IGF-1C), a 12-amino acid sequence GYGSSSRRAPQT, has been identified as the active region of IGF-1 protein 22 and is relevant to promotion of healing of corneal epithelial wounds. 19 This evidence leads to our hypothesis that IGF-1C possesses therapeutic effects similar to those of their full-length counterparts.…”

Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD

“…As reviewed by Zoccali (11), many biomarkers have been tested in the dialysis population, including ferritin (17), high-sensitivity C-reactive protein (hsCRP) (18)(19)(20)(21)(22), IGF-1 (23,24), IL-6 (18,22,25), soluble intracellular adhesion molecule (sICAM-1), soluble vascular cellular adhesion molecule 1 (sVCAM-1) (26,27), troponin T (TnT) (28), TNF (29), platelet count (PLT) (30), and white blood cell (WBC) (31). These risk biomarkers have each been shown to independently predict both clinical CVD and mortality in ESRD, but they often rely on relatively small materials, and multivariate testing and adjustment for common confounders, such as residual renal function, have not been performed consistently.…”