Vaspin levels are significantly higher in women, and gender is an independent predictor of circulating vaspin in both control and CD patients. In addition, age independently predicts vaspin in control patients, whereas GFR and CRP are independently associated with this adipokine in CD patients. In contrast, circulating vaspin is not independently associated with markers of glucose and lipid metabolism.

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.

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) Ͼ50 ml/min.RESEARCH DESIGN AND METHODS -FGF21 was determined by enzyme-linked immunosorbent assay in control (n ϭ 60) and CD (n ϭ 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 Ͼ15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR Ͼ50 ml/min (201.9 ng/l) (P Ͻ 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P Ͻ 0.05).CONCLUSIONS -FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects. Diabetes Care 32:126-128, 2009R ecently, fibroblast growth factor 21 (FGF21) was introduced as a novel adipokine with potent antidiabetic properties (1-4). In contrast to extensive experiments in animals, only one study to date has determined regulation and function of FGF21 in humans in vivo (5), and no data have been published about the relation of this adipokine to renal function. RESEARCH DESIGN AND METHODS -The design of the study has been described in detail recently (6 -8). Briefly, 120 Caucasian men (n ϭ 62) and women (n ϭ 58) were recruited with 60 patients having a glomerular filtration rate (GFR) Ͼ50 ml/min (control subjects) as assessed by the original Modification of Diet in Renal Disease formula (9) and 60 patients being on chronic hemodialysis (CD). A total of 30 control subjects and 32 CD patients had type 2 diabetes. The study was approved by the local ethics committee, and all subjects gave written informed consent before taking part in the study. AssaysBlood samples were taken after an overnight fast. In CD patients, blood was drawn just before hemodialysis started. FGF21 (Biovendor, Modrice, Czech Republic), adiponectin (Mediagnost, Reutlingen, Germany), and leptin (Mediagnost) were determined with enzyme-linked immunosorbent assays according to the manufacturer's instructions. Statistical analysisStatistical analyses are specified in RESULTS and in the Table 1 legend. Table 1 summarizes clinical characteristics of the subgroups studied (control, CD) further divided into nondiabetic and diabetic subjects. Median circulating FGF21 was Ͼ15-fold higher in CD patients (3,710.6 Ϯ 5,541.3 ng/l) compared with control subjects (201.9 Ϯ 275.5 ng/l) (P Ͻ 0.001) ( Table 1). Furthermore, FGF21 serum levels were significantly higher in men (1,959.0 Ϯ 4,505.5 ng/l) compared with women (446.9 Ϯ 1,609.0 ng/l) (P Ͻ 0.05) but did not depend on type 2 diabetes. RESULTS FGF21 serum levels are increased in CD patients Univariate correlationsUsing the Spearman's rank correlation method, serum FGF21 concentrations positively correlated with BMI (r ϭ 0.33, 95% CI 0.08 -0.54, P ϭ ...

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We demonstrate that circulating FGF-21 is increased in both CKD and AKD. Our results suggest renal excretion as a major route for FGF-21 elimination. The pathophysiological significance of these findings needs to be elucidated in more detail.

OBJECTIVEProgranulin 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 METHODSProgranulin 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).RESULTSMedian 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.CONCLUSIONSWe 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.

End-stage renal disease (ESRD) of undetermined etiology is highly prevalent and constitutes a significant clinical challenge, particularly in the context of kidney transplantation (KT). Despite the identification of numerous rare hereditary nephropathies over the last few decades, patients with undetermined ESRD are not being systematically investigated for rare genetic causes in clinical practice. To address this, we utilized mutation analysis in patients on the kidney transplant waitlist and scrutinized underlying renal diagnoses of 142 patients in a single center KT-waitlist. This cohort was stratified into 85 cases of determined and 57 cases of undetermined ESRD. The latter patients were analyzed by a renal gene panel for mutations in 209 genes associated with ESRD. The most likely genetic diagnoses in 12% of the tested individuals with undetermined ESRD were established. All of these patients showed mutations in genes encoding components of the glomerular filtration barrier. Taken together, hereditary nephropathies, including autosomal dominant polycystic kidney disease, were identified in 35 of the 142 patients of the waitlist cohort. By significantly increasing the proportion of hereditary diagnoses from 29 to 35 patients, the rate of undetermined ESRD significantly decreased from 57 to 51 patients. This study demonstrates the beneficial use of genetic diagnostics in significantly unraveling undetermined ESRD cases prior to KT. Thus, in the absence of renal histology or the presence of unspecific histological conditions, such as hypertensive nephrosclerosis, focal segmental glomerulosclerosis or thrombotic microangiopathy, genetic analysis may provide a robust and specific renal diagnosis and allow for optimizing pre-and post-KT management.

OBJECTIVE -Retinol-binding protein (RBP)-4 was recently identified as an adipokine that induces insulin resistance. In the current study, we investigated RBP-4 serum levels in diabetic and nondiabetic patients on chronic hemodialysis (CD) compared with control subjects with a glomerular filtration rate Ͼ50 ml/min. The majority of the diabetic subjects used oral hypoglycemic agents or insulin.RESEARCH DESIGN AND METHODS -RBP-4 was determined by enzyme-linked immunosorbent assay in control subjects (n ϭ 59) and CD patients (n ϭ 58) and correlated with clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.RESULTS -Mean serum RBP-4 levels were almost fourfold higher in CD patients (102 Ϯ 30 mg/l) compared with control subjects (28 Ϯ 8 mg/l). Furthermore, serum creatinine independently predicted RBP-4 concentrations in multiple regression analyses in both control subjects and CD patients. In addition, C-reactive protein and systolic blood pressure independently and negatively correlated with RBP-4 serum concentrations in CD patients but not control subjects. In contrast, markers of glucose and lipid metabolism were not independently related to serum RBP-4 in control subjects or CD patients.CONCLUSIONS -We show that markers of renal function are independently related to serum RBP-4 levels.