Blood and lymphatic vessels in children with chronic kidney disease
Research type
Research Study
Full title
Investigating how blood and lymphatic vessels change in children with chronic kidney disease.
IRAS ID
308472
Contact name
Rukshana Shroff
Contact email
Sponsor organisation
Great Ormond Street Hospital NHS Foundation Trust
Duration of Study in the UK
4 years, 1 months, 31 days
Research summary
Cardiovascular disease is the most common cause of death in people with advanced kidney disease and even young adults on dialysis have the mortality risk of an octogenarian. Using a model of intact arteries, removed at the time of routine surgery in children with kidney disease, we have shown that calcification or 'furring up' of the vessel along with extensive damage to the cells of the vessel wall are present even in young children on dialysis. These vessel changes lead to stiffness of the major arteries and heart failure. The original studies have given us insights into mechanisms of vessel wall damage and calcification, but also introduced several new areas of research. In particular we have found that this damage includes DNA damage, premature ageing and senescence of the vascular smooth muscle cells in the vessel wall. In addition, our more recent work has begun to identify that lymphatics play a fundamental role in renal physiology and pathology, and treatments modulating these vessels have therapeutic potential across the spectrum of kidney disease.
We will perform laboratory studies to assess the changes that occur as the vessels become damaged so that we can understand what cellular pathways become disrupted and therefore potentially identify novel therapies. We will examine the effects of medications, hormones and growth factors which promote or inhibit changes in blood or lymphatic vessels from patients with kidney failure. These substances include drugs, inflammatory factors and naturally occurring hormones, growth factors and chemicals that are perturbed in kidney failure and dialysis.
We hope that these studies will lead to a better understanding of how blood and lymphatics change in children with chronic kidney disease and help to develop future therapies to decrease the risk of death in patients with kidney failure.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
23/WM/0254
Date of REC Opinion
20 Dec 2023
REC opinion
Further Information Favourable Opinion