This is a renewal application for the Clinical and Translational Core of the UT Southwestern George M. O'Brien Kidney Disease Center. The long-term, broad objective of this core is to facilitate translation of basic and clinical discoveries into effective diagnostic and therapeutic strategies to improve the lives of patients with chronic kidney disease (CKD). Over the past 4.5 years we established the Core as an outstanding resource for Center investigators to conduct studies in patients with CKD including those diabetes, hypertension and glomerular diseases. Center investigators have conducted innovative, high impact cuttingedge research in diverse ethnic and racial groups to improve detection, diagnosis, prevention and treatment of those at very high risk for kidney disease progression and its complications. We now propose the following four specific aims: 1) provide expertise in study design, and protocol development and implementation including regulatory knowledge, grants and contracts, database management and biostatistics and coordination of these functions with other Cores and Center Investigators;2) provide technical and logistical support for conducting human clinical trials including study subject recruitment and retention, data collection, adverse event reporting, study drug randomization allocation and storage, body fluid collection, processing and storage for phase 1-4 clinical trials;3) develop a new assay for Klotho protein and novel renal magnetic resonance imaging methods in conjunction with the cell biology and imaging core, provide measurements of cardiovascular and renal function including central aortic and ambulatory blood pressure, flow-mediated vasodilation, creatinine and iothalamate measurements and ELISA methods for markers of kidney injury, and design and statistical analysis of human genetic studies including linkage analysis, whole-exome sequencing, and candidate gene analysis;and 4) provide educational enrichment programs for all Center investigators and their trainees. The C&T Core is critical to the overall goal of the UTSW O'Brien Kidney Center. The Core is operational and poised to promote the discovery and application of research methods leading to improved health and well-being of patients with chronic kidney disease.
Chronic kidney disease is a major public health problem that affects nearly 13% of the United States adult population. Chronic kidney disease often progresses to kidney failure necessitating treatment with dialysis or kidney transplantation and is associated with premature death often due to cardiovascular complications such as heart attack and stroke. Development of new research methods and their application is critical to improve the detection, diagnosis, prevention and treatment of chronic kidnev disease and its complications.
|Raman, Archana; Reif, Gail A; Dai, Yuqiao et al. (2017) Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease. J Am Soc Nephrol 28:2708-2719|
|Yano, Yuichiro; Neeland, Ian J; Ayers, Colby et al. (2017) Hemodynamic and Mechanical Properties of the Proximal Aorta in Young and Middle-Aged Adults With Isolated Systolic Hypertension: The Dallas Heart Study. Hypertension 70:158-165|
|Hajarnis, Sachin; Lakhia, Ronak; Yheskel, Matanel et al. (2017) microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism. Nat Commun 8:14395|
|Van Buren, Peter Noel (2017) Pathophysiology and implications of intradialytic hypertension. Curr Opin Nephrol Hypertens 26:303-310|
|Pan, Xinchao; Karner, Courtney M; Carroll, Thomas J (2017) Myc cooperates with ?-catenin to drive gene expression in nephron progenitor cells. Development 144:4173-4182|
|Wang, Qian; Cobo-Stark, Patricia; Patel, Vishal et al. (2017) Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease. Kidney Int :|
|Sanghera, Prateek; Ghanta, Mythili; Ozay, Fatih et al. (2017) Kidney Diseases Associated With Alternative Complement Pathway Dysregulation and Potential Treatment Options. Am J Med Sci 354:533-538|
|Kim, Ji-Hee; Xie, Jian; Hwang, Kyu-Hee et al. (2017) Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes. J Am Soc Nephrol 28:140-151|
|Wu, Yueh-Lin; Xie, Jian; An, Sung-Wan et al. (2017) Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho. Kidney Int 91:830-841|
|Ku, Elaine; Gassman, Jennifer; Appel, Lawrence J et al. (2017) BP Control and Long-Term Risk of ESRD and Mortality. J Am Soc Nephrol 28:671-677|
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