Serum Phosphate: Effects on Vascular and Endothelial Function

Patients with chronic kidney disease (CKD) are at greatly increased risk of premature cardiovascular disease. Phosphate, a mineral, is often elevated in CKD and this is a risk factor for cardiovascular disease but the mechanism of action is unclear. Phosphate is modifiable with dietary and drug interventions and is potentially an important therapeutic target to reduce cardiovascular risk in patients with CKD. 

Dr Kate Stevens is studying the effects of elevated phosphate on blood vessel and cell function both in the laboratory and in a clinical setting with a view to better understanding its mechanism of action as a cardiovascular risk factor. This information could help to provide a basis for a trial to compare phosphate lowering interventions.

There are 3 components to the research: cellular studies, vessel studies and a clinical study. The work is predominantly laboratory based and utilises a number of scientific techniques including cell culture, wire myography, gene expression with PCRand microarray and protein detection and quantification with ELISA and Western blot. Clinical techniques include flow mediated dilation and pulse wave velocity and analysis.

Thus far we have seen that exposing cells and vessels to elevated phosphate alters cell growth and impairs endothelial function and this effect does not seem to relate to changes in intra-cellular calcium. In human subjects phosphate loading impairs endothelial function. Ongoing work includes studying reactive oxygen species in human subjects with and without kidney disease and in cells and vessels exposed to high concentrations of phosphate.

Publications

1. Stevens KK, Woo YM,  Rodger RSC and Geddes CC. Discharging patients from the renal clinic to primary care – will they get appropriate monitoring of renal function? The Quarterly Journal of Medicine 2009;102:425-8.
2. Stevens KK, Patel RK, Clancy MJ and Jardine AG. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are associated with slow graft function following live donor renal transplantation. Transplantation. 2010;89:707-9.
3. Patel RK, Jardine AMG, Mark PB, Cunningham AF, Steedman T, McQuarrie EP, Powell JR, Stevens KK, Dargie HJ, and  Jardine AG. Association of left atrial volume with mortality among end stage renal disease patients with left ventricular hypertrophy referred for renal transplantation. Am J Kidney Dis. 2010;55:1088-96.
4. Mark PB, Stevens KK, Jardine AG.  Electrolytes: Acid-base. The Encyclopaedia of Human Nutrition (3rd Edition). Oxford: Elsevier
5. Stevens KK, Morgan IR, Patel RK, Mark PB, Geddes CC, Jardine AG, Delles C. Serum Phosphate and outcome at one year post deceased donor renal transplantation. Clin Transplant. 2011;25:e199-204
6. Stevens KK, Woo YM, McClure JD, Fox JG, Geddes CC. Deceased donor transplantation in the elderly – are we creating false hope? Nephrol Dial Transplant. 2011;26:2382-6.
7. Stevens KK and Jardine AG SHARP: a stab in the right direction in chronic kidney disease Lancet. 2011;377:2153-4
8. Stevens KK, McQuarrie EP, Sands W, Hillyard DZ, Patel RK, Mark PB and AG Jardine.  Fibroblast growth factor 23 predicts left ventricular mass and induces cell adhesion molecule formation. Int J Nephrol. 2011;2011:297070.
9. Stevens KK, Patel RK and Jardine AG. How to identify and manage diabetes mellitus after renal transplantation. Journal of Renal Care 2012;38: 125-137
10. Patel RK, McQuarrie EP, Mark PB, Stevens KK and Jardine AG. Altered relative concentrations of high energy phosphates in uremic cardiomyopathy measured by magnetic resonance spectroscopy. Nephrol Dial Transplant 2012;27:2446-2451