Copeptin in Adolescent Participants With Type 1 Diabetes and Early Renal Hemodynamic Function
Status:
Completed
Trial end date:
2021-08-01
Target enrollment:
Participant gender:
Summary
Over 1.25 million Americans have type 1 diabetes (T1D), increasing risk for early death from
cardiorenal disease. The strongest risk factor for cardiovascular disease (CVD) and mortality
in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia
and hypertension, are beneficial, but only partially protect against DKD.
Hyperfiltration is common in youth with T1D, and predicts progressive DKD. Hyperfiltration is
also associated with early changes in intrarenal hemodynamic function, including increased
renal plasma flow (RPF) and glomerular pressure. Intrarenal hemodynamic function is strongly
influenced by the renin-angiotensin-aldosterone system (RAAS), which is also considered a key
player in the pathogenesis of DKD. Preliminary data demonstrate differences in intrarenal
hemodynamic function and RAAS activation in early and advanced DKD in T1D. However, the
pathophysiology contributing to the differences observed in RAAS activation and intrarenal
hemodynamic function in T1D are poorly defined Animal research demonstrates that arginine
vasopressin (AVP) acts directly to modify intrarenal hemodynamic function, but also
indirectly by activating RAAS. Preliminary data suggest that elevated copeptin, a marker of
AVP, which predicts DKD in T1D adults, independently of other risk factors. However, no human
studies to date have examined how copeptin relates to intrarenal hemodynamic function in
early DKD in T1D. A better understanding of this relationship is critical to inform
development of new therapies targeting the AVP system in T1D. Accordingly, in this study, the
investigators propose to define the relationship between copeptin and intrarenal hemodynamics
in early stages of DKD, by studying copeptin levels, renal plasma flow, and glomerular
filtration in youth (n=50) aged 12-21 y with T1D duration < 10 y.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
University of Colorado Denver School of Medicine Barbara Davis Center