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Results for “Renalase”

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PubMed2005

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure.

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.

Animals↗

PubMed2026

Assay-dependent variability in peptide biomarker quantification: experimental evidence from renalase in chronic kidney disease.

BACKGROUND: Renalase is a promising biomarker for kidney disease, but published levels vary widely between studies. We hypothesised that variability in commercial enzyme-linked immunosorbent assays (ELISAs) kits and matrix effects (serum vs plasma) drive these inconsistencies. METHODS: Paired serum and plasma samples from 56 participants (28 chronic kidney disease (CKD) stages 2-5, 28 healthy controls) were tested using three commercial renalase ELISAs (BTLAB, Cloud-Clone, EIAab). We assessed intra-assay precision, inter-assay agreement (Spearman's rank correlation and Bland-Altman analysis on log10-transformed values), matrix effects, and associations with estimated glomerular filtration rate (eGFR). Diagnostic performance was evaluated by Receiver operating characteristic (ROC) analysis. RESULTS: Inter-assay renalase concentrations differed markedly (up to orders of magnitude), with weak inter-assay correlations (r ≤ 0.25). Bland-Altman analyses revealed large, systematic biases between kits. Only the BTLAB assay showed consistent serum/plasma agreement, a significant correlation with eGFR (ρ ≈ 0.32-0.42, p < 0.05), and moderate discriminatory performance for CKD in serum (AUC = 0.70) and plasma (AUC = 0.68). Cloud-Clone and EIAab produced divergent results and strong matrix-dependent biases. CONCLUSIONS: Observed variability among commercial ELISA platforms may compromise comparability between studies. Harmonisation, standardised reference materials, and cross-validation are necessary before renalase assays can be used reliably in clinical practice.

Humans↗

PubMed2007

Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population.

Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is secreted by the kidney, degrades circulating catecholamines, and modulates cardiac function and systemic blood pressure (BP). Its discovery may provide novel insights into the mechanisms of BP regulation and the pathogenesis of essential hypertension (EH). We designed a two-stage case-control study to investigate whether the renalase gene harbored any genetic variants associated with EH in the northern Han Chinese population. From the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317 hypertensive cases and 1,269 normotensive controls were recruited. These total 2,586 subjects were taken as the main study population in this study. In stage 1, all the eight selected single nucleotide polymorphisms (SNPs) of the renalase gene were genotyped and tested within a subsample (503 cases and 490 controls) of the main study population. By single locus analyses, three SNPs, rs2576178, rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In stage 2, these three SNPs were genotyped on the remaining individuals and analyzed using all the individuals. After Bonferroni correction for multiple comparisons, the associations of rs2576178 and rs2296545 with EH were still significant in stage 2. The cases had higher frequencies of rs2576178 G allele and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61 versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95% CI, 1.25 to 2.00; P = 0.0002) and 1.61 (95% CI, 1.26 to 2.04; P = 0.0002), respectively. We also found risk-associated haplotypes and diplotypes, which further confirmed the significant association between the renalase gene and EH. These findings may provide novel genetic susceptibility markers for EH and lead to a better understanding of EH pathophysiology. In addition, further replications in other populations and functional studies would be warranted.

Adult↗

PubMed2005

Renalase, a catecholamine-metabolizing hormone from the kidney.

A novel flavin adenine dinucleotide-dependent amine oxidase that is secreted by the kidney, circulates in the blood, and modulates cardiac function and systemic blood pressure has recently been discovered. Renalase appears to be a hormone that metabolizes catecholamines, and its discovery will facilitate our understanding of sympathetic regulation.

Animals↗

PubMed2005

Hypertension in dialysis.

PURPOSE OF REVIEW: Hypertension is highly prevalent in dialysis patients and may be important to the high cardiovascular mortality of this population. This review shows the current direction in dialysis-associated hypertension management. RECENT FINDINGS: Decreasing dialysate sodium concentration based on pre-hemodialysis plasma sodium concentration may have an additive effect in controlling hypertension. Sympathetic nervous system overactivity is an important feature of end-stage renal disease; a new amine oxidase, renalase, may be relevant to the pathogenesis of hypertension in this population. Similarly, drugs that block the sympathetic nervous system are uniformly protective in dialysis patients. Daily dialysis (short or long) results in better blood pressure control, and the mechanisms resulting in this effect are increasingly better understood. SUMMARY: Long-term control of hypertension is necessary in dialysis patients. The better understanding of the dialysis-associated hypertension pathogenesis has impact on the dialysis prescription and antihypertensive drug choices.

Hemodialysis Solutions↗

PubMed2006

Epidemiology of non-dialysis-requiring chronic kidney disease and cardiovascular disease.

PURPOSE OF REVIEW: To review recent literature about the relationship between non-dialysis-requiring chronic kidney disease and cardiovascular disease as well as possible explanatory factors. RECENT FINDINGS: Reduced estimated glomerular filtration rate below 60 ml/min/1.73 m independently predicts the risk of death and cardiovascular events in persons with or without known cardiovascular disease as well as those undergoing coronary or peripheral arterial revascularization. This risk is not linearly associated with level of kidney function. Chronic kidney disease is associated with a larger burden of traditional vascular risk factors but is also linked to abnormalities in a variety of nontraditional pathways such as dysregulation of mineral metabolism and arterial calcification, vessel stiffness and endothelial dysfunction, insulin resistance, inflammation, malnutrition, and anemia, among others. Other novel kidney-specific proteins (e.g. renalase) may play direct mediating roles. The relative contribution of these factors to excess cardiovascular disease in chronic kidney disease remains unclear. SUMMARY: Recent evidence demonstrates the importance of non-dialysis-requiring chronic kidney disease as a potent predictor of cardiovascular disease and its complications. Randomized trials should be performed to determine whether modification of traditional and nontraditional risk factors can reduce incident cardiovascular disease as well as which interventions can optimize treatment outcomes in persons with chronic kidney disease and cardiovascular disease.

Cardiovascular Diseases↗