Preparation for hypertension specialists : genomics reveals the pathogenesis of hypertension

Genomics is a discipline in genetics that applies recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes, the complete set of DNA within a single cell of an organism. Research into the genetics of hypertension has now expanded to genomics. Two approaches have dominated this field. One relies on large populations in which the phenotype, hypertension versus no hypertension, or hypertension-relevant phenotypes are compared. Genome-wide association (GWAS) analyses of (>1 million) common variants identify relevant loci and possible genes exerting small effects. Detailed studies on APOL1 and SH2B3 are opening entire new fields of research. Family-based Mendelian studies have identified rare variants that exert very large effects on blood pressure. Mechanistically these studies have been a bonanza of new information. The approaches are complementary

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

Biomarkers and predicting acute kidney injury

AIM: How can we convert biomarkers into reliable, validated laboratory tests? GFR estimators exist for more than a century. The first utilitarian biomarkers were endogenously produced urea and creatinine. Clinicians then developed simple tests to determine whether or not renal tubular function was maintained. Are there faster and better tests that reflect decreased renal function and increased acute kidney injury (AKI) risk? METHODS: We inspect earlier, and recently propagated biomarkers. Cystatin C reflects GFR and is not confounded by muscle mass. Direct GFR and plasma volume can now be measured acutely within 3 h. Better yet would be tests that give information before GFR decreases and prior to urea, creatinine, and cystatin C increases. Prospective tests identifying those persons likely to develop AKI would be helpful. Even more utilitarian would be a test that also suggests a therapeutic avenue. RESULTS: A number of highly provocative biomarkers have recently been proposed. Moreover, the application of big data from huge electronic medical records promise new directions in identifying and dealing with AKI. CONCLUSIONS: Pipedreams are in the pipeline; the novel findings require immediate testing, verification, and perhaps application. Future research promises to make such dreams come true

Mutant Cullin causes cardiovascular compromise

Mendelian hypertension is rare; however, Mendelian syndromes have taught us an amazing amount about mechanisms of distal sodium and chloride reabsorption, as well as how systemic hypertension might come about. In this issue of EMBO Molecular Medicine, Schumacher et al (2015) present a mouse model of the Cullin‐3 (CUL3Δ403–459) mutation, which causes a form of pseudohypoaldosteronism type‐2 (PHA‐2). CUL3 is involved in ubiquitination. Surprising is the severity of the hypertension, which may be explained in part on the basis of CUL3 actions in vascular cells. The findings underscore the role of "cleanup" in the maintenance of normal physiology