Anette Bachmann

Serum Levels of the Adipokine FGF21 Depend on Renal Function

OBJECTIVE—To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) >50 ml/min. RESEARCH DESIGN AND METHODS—FGF21 was determined by enzyme-linked immunosorbent assay in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups. RESULTS—Median serum FGF21 levels were >15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR >50 ml/min (201.9 ng/l) (P < 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P < 0.05). CONCLUSIONS—FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects.

Serum levels of the myokine irisin in relation to metabolic and renal function.

OBJECTIVE Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied. DESIGN AND METHODS Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD). RESULTS Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis. CONCLUSIONS We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.

Serum Levels of the Adipokine Chemerin in Relation to Renal Function

OBJECTIVE To investigate serum levels of the adipokine chemerin in patients on chronic hemodialysis (CD) as compared with control patients with a glomerular filtration rate (GFR) >50 ml/min. RESEARCH DESIGN AND METHODS Chemerin was quantified by ELISA in control patients (n = 60) and CD patients (n = 60) and correlated with clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups. RESULTS Median serum chemerin levels were more than twofold higher in CD patients (542.2 μg/l) compared with subjects with a GFR >50 ml/min (254.3 μg/l) (P < 0.001). Furthermore, GFR, as assessed by the original Modification of Diet in Renal Disease formula, independently predicted circulating chemerin concentrations in multiple regression analyses in both control patients (P < 0.05) and CD patients (P < 0.01). CONCLUSIONS We demonstrate that markers of renal function are independently related to circulating chemerin levels.

Serum levels of fibroblast growth factor-21 are increased in chronic and acute renal dysfunction

Fibroblast growth factor (FGF)‐21 has recently been introduced as a circulating adipokine which reverses insulin resistance and obesity in rodents. In this study, regulation of FGF‐21 in renal dysfunction was elucidated in both chronic kidney disease (CKD) and acute kidney dysfunction (AKD).

Circulating Angiopoietin-like Protein 8 Is Independently Associated With Fasting Plasma Glucose and Type 2 Diabetes Mellitus

OBJECTIVE Angiopoietin-like protein 8 (Angptl8) has recently been introduced as a novel adipokine/hepatokine that promotes pancreatic β-cell proliferation and improves glucose tolerance in mouse models of insulin resistance. However, regulation of Angptl8 in human type 2 diabetes mellitus (T2DM) and renal dysfunction has not been determined. RESEARCH DESIGN AND METHODS Serum Angptl8 levels were quantified by ELISA in 62 patients with T2DM as compared with 58 nondiabetic subjects in vivo. Within both groups, about half of the patients were on chronic hemodialysis or had an estimated glomerular filtration rate above 50 mL/min/1.73 m(2). Furthermore, we investigated the effect of insulin and differentiation on Angptl8 mRNA expression in 3T3-L1 adipocytes in vitro. RESULTS Median [interquartile range] serum Angptl8 levels were higher in patients with T2DM (1.19 [0.37] μg/L) as compared with nondiabetic subjects (1.03 [0.47] μg/L) (P = .005). Furthermore, the adipokine/hepatokine was significantly higher in women (1.21 [0.47] μg/L) as compared with men (1.05 [0.44] μg/L]) (P = .013). In multivariate analysis, fasting glucose and T2DM but not renal function remained independent and positive predictors of circulating Angptl8 even after adjustment for markers of obesity, lipid status, and inflammation (P < .05). Furthermore, Angptl8 mRNA expression was induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro. CONCLUSIONS Circulating Angptl8 is positively and independently associated with T2DM and fasting glucose in vivo. Furthermore, Angptl8 mRNA expression is induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.

Serum Levels of the Adipokine Progranulin Depend on Renal Function

OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD). RESULTS Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. CONCLUSIONS We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin.

Serum levels of the adipokine zinc-α2-glycoprotein are increased in chronic hemodialysis

Zinc-α2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight control. In the current study, we investigated renal elimination of this adipokine by comparing circulating ZAG levels in patients on chronic hemodialysis (CD) with controls. Sixty CD patients and 60 controls with a glomerular filtration rate greater than 50 mL/min were included. Serum concentrations of ZAG were determined by enzyme-linked immunosorbent assay; and its relationship with renal function, glucose and lipid metabolism, as well as inflammation was studied in both groups. Median ZAG serum levels were almost 2-fold higher in CD patients (94.4 ± 29.4 mg/L) as compared with controls (48.3 ± 23.5 mg/L) (P < .001). Furthermore, circulating ZAG was negatively correlated with fasting insulin, homeostasis model assessment of insulin resistance, and leptin in controls in univariate analysis. Moreover, CD independently predicted ZAG concentrations in multiple regression analysis. Renal filtration appears to be an important route of ZAG elimination, and markers of renal function should be included in studies on ZAG physiology.

Serum levels of angiopoietin-related growth factor in diabetes mellitus and chronic hemodialysis

Angiopoietin-related growth factor (AGF) was recently introduced as a novel liver-derived protein that antagonizes obesity and insulin resistance. In the current study, we investigated circulating AGF levels in relation to renal function and type 2 diabetes mellitus (T2DM). Angiopoietin-related growth factor was determined by enzyme-linked immunosorbent assay in subjects with a glomerular filtration rate greater than 50 mL/min (n = 60, 30 diabetic and 30 nondiabetic) and in patients on chronic hemodialysis (CD; n = 60, 32 diabetic and 28 nondiabetic). Furthermore, AGF was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. Median serum AGF levels were significantly lower in CD patients (125.9 +/- 96.3 microg/L) as compared with subjects with a glomerular filtration rate greater than 50 mL/min (164.0 +/- 95.4 microg/L) (P < .05). Furthermore, AGF serum levels were significantly increased in diabetic patients (161.7 +/- 114.2 microg/L) as compared with nondiabetic subjects (123.0 +/- 88.2 microg/L) (P < .01). Moreover, CD negatively and T2DM positively predicted AGF concentrations in multiple regression analysis. In addition, fasting serum glucose was independently and positively correlated with circulating AGF in all patients and controls. Our results suggest that renal dysfunction is negatively and T2DM is positively associated with AGF serum levels. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.

Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis

Adipokines including leptin, adiponectin, visfatin, resistin, and interleukin (IL)-6 significantly influence energy metabolism, insulin sensitivity, and cardiovascular health. In the current study, we investigated serum levels of these adipokines in diabetic and nondiabetic patients on maintenance hemodialysis (MD) as compared with controls with a glomerular filtration rate greater than 50 mL/min. Serum leptin, adiponectin, high-molecular-weight (HMW) adiponectin, visfatin, resistin, and IL-6 were determined by enzyme-linked immunosorbent assay in control (n = 60) and MD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. Adiponectin, visfatin, resistin, and IL-6 were significantly elevated in MD patients as compared with controls. In multivariate analyses, sex and body mass index were independently correlated with serum leptin levels in both controls and MD patients. Furthermore, insulin resistance was independently and negatively associated with adiponectin and HMW adiponectin in both groups. Moreover, circulating resistin levels were independently correlated with serum visfatin concentrations in control and MD patients. However, various independent associations were only found in either controls or patients on MD. Thus, serum IL-6 levels were strongly and independently associated with C reactive protein and resistin in MD patients but not control subjects. We show that levels of various adipokines are significantly increased in MD patients. Furthermore, regulation of adipokines in vivo strongly depends on renal function. Regulation of HMW adiponectin is similar as compared with total adiponectin in the patients studied.

Serum levels of adipocyte fatty acid-binding protein (AFABP) are increased in chronic haemodialysis (CD)

Objective  Adipocyte fatty acid‐binding protein (AFABP) was recently introduced as an adipocyte‐expressed factor, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In the current study, we investigated renal elimination of this protein by comparing circulating AFABP levels in patients on chronic haemodialysis (CD) with controls. We hypothesized that if renal filtration is a significant route of elimination of AFABP, it would accumulate in CD patients.