AimsPatients with chronic heart failure are often characterized by impaired renal function, also referred to as cardiorenal syndrome (CRS). The aim of this study was to assess whether novel markers of kidney injury are elevated in chronic heart failure and CRS. Methods and resultsThe new renal biomarkers kidney injury molecule-1 (KIM-1), N-acetyl-ß-D-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed from urine samples of 173 individuals. Patients with chronic heart failure (n ¼ 150) were characterized by decreased ejection fraction (32 + 9% vs. controls 62 + 4%, P , 0.001) and increased plasma N-terminal pro-brain natriuretic peptide (median 1460 pg/mL, interquartile range (IQR) 630 -3000 pg/mL vs. controls 56, IQR 25 -64l pg/mL, P , 0.001). Urinary analysis showed that KIM-1 was significantly elevated in heart failure patients compared with healthy controls (1100, IQR 620-1920 vs. 550, IQR 320 -740 ng/g urinary creatinine, P , 0.001). Further, KIM-1 increased significantly with decreasing left ventricular function (r ¼ 20.37, P , 0.001) and severity of New York Heart Association (NYHA)-class (r ¼ 0.5, P , 0.001). N-acetyl-ß-D-glucosaminidase showed a weaker response but correlated significantly with left ventricular dysfunction (r ¼ 20.18, P ¼ 0.015) and more severe clinical condition (r ¼ 0.22, P ¼ 0.04). In contrast, NGAL showed no significant correlation. Kidney injury molecule-1 and NAG were also predictors of all-cause mortality and the composite of all-cause mortality and rehospitalization for heart failure (all P , 0.05). ConclusionsKidney injury molecule-1 and NAG are elevated in symptomatic heart failure. This finding may be present in patients with apparently normal kidney function and indicates tubular injury in chronic heart failure. Kidney injury molecule-1 and NAG are potential markers of CRS with additional prognostic value.--

Adiponectin exerts a NO-dependent vasodilation in resistance arteries of normoglycemic ZL rats, but not diabetic ZDF rats. This may contribute to endothelial dysfunction in ZDF rats. Alterations in the expression of APPL1 may be involved in the observed insensitivity to adiponectin in ZDF rats.

BackgroundGenome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes.MethodsWe performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks.ResultsAll of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats.ConclusionThe expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant.