Chronic kidney disease (CKD) is associated with a marked increase in risk for cardiovascular disease (CVD), such that patients with CKD are more likely to die from CVD than to progress to end-stage renal disease. Hypertension (HTN) amplifies risk for CVD and affects more than 1 billion people worldwide. However, the causes of HTN cannot be determined in most patients and the mechanisms underlying the complex interactions among the kidney, HTN and cardiovascular disease and subsequent risk for mortality are not clear. We suggest that precise definition of these mechanisms will require multi-disciplinary teams with expertise in renal and cardiovascular systems. Accordingly, our objective is to provide a panel of sophisticated tools to support and facilitate multi-disciplinary, basic discovery research in animal models on the unique links relating the kidney, cardiovascular disease and HTN. The Core is configured to provide access to a range of experimental models of kidney, heart and vascular diseases, and Core personnel have comprehensive expertise in utilizing mouse models of CKD, CVD, and HTN, as well as functional kidney and cardiovascular screens in non-mammalian models. The Core will serve kidney or cardiovascular investigators who may be working in isolation to raise their awareness of the clinical impact of the heart-kidney axis and to provide access to models and techniques that can entice them to expand their efforts into our broader area of thematic interest. We will provide comprehensive phenotyping services for kidney, blood pressure and other cardiovascular functions. The scope of the Core will be Regional, National and International. Core staff will assist in experimental design as well as data collection and analysis. Capabilities of the Core will also be useful for determining functional relevance of genetic variants discovered in studies based in the Renal Genomics Core as well as providing preliminary data for human studies in the Clinical and Translational Core. The Animal Models Core has four specific aims: (1) to provide access to mouse models of CKD, HTN, and CVD;(2) to provide state-of-the-art kidney and cardiovascular phenotyping in mice;(3) to generate models of kidney cross-transplantation for distinguishing renal and systemic contributions to physiologic, metabolic and/or immunological functions in mice;and (4) to provide rapid screens in zebrafish for genetic variants with functional effects in kidney and/or cardiovascular system.
The Animal Core will offer both mammalian and non-mammalian models and phenotyping services to investigators studying the mechanisms connecting hypertension, kidney disease and heart disease. The capabilities of the Animal Core will also align with the genetic and human studies offered by the Center's other Cores.
|Inrig, Jula K; Califf, Robert M; Tasneem, Asba et al. (2014) The landscape of clinical trials in nephrology: a systematic review of Clinicaltrials.gov. Am J Kidney Dis 63:771-80|
|Tan, Minjia; Peng, Chao; Anderson, Kristin A et al. (2014) Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab 19:605-17|
|Ortiz-Melo, David I; Spurney, Robert F (2014) Special deLIVERy: podocyte injury promotes renal angiotensin II generation from liver-derived angiotensinogen. Kidney Int 85:1009-11|
|Pálsson, Ragnar; Patel, Uptal D (2014) Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis 21:273-80|
|Patel, Uptal D (2014) Outcomes after pediatric kidney transplantation improving: how can we do even better? Pediatrics 133:734-5|