HDL from CDK Patients Loses Vasoprotective Effects

Share this article:
HDL from dialysis patients did not decrease apoptosis of endothelial cells.
HDL from dialysis patients did not decrease apoptosis of endothelial cells.

PRAGUE—HDL cholesterol (HDL) in patients with chronic kidney disease (CKD) loses its protective effect on vascular endothelium, new findings suggest. Rather than supporting the beneficial functions of the endothelium, it appears to become pro-inflammatory and inhibit them.

Timo Speer, MD of Saarland University Hospital in Homburg/Saar, Germany, reported his results of in vitro and animal testing of HDL here at the 48th  Congress of the European Renal Association-European Dialysis and Transplant Association.

Previous work has shown that as estimated glomerular filtration rates decrease, the rate of cardiovascular events increases, long before patients need dialysis. “So kidney disease is a cardiovascular risk factor per se,” Dr. Speer told listeners.

In healthy people, HDL has antioxidant, anti-inflammatory, and antithrombotic effects at the level of the endothelium and promotes nitric oxide (NO) production and endothelial regeneration. Epidemiologic studies have shown a 3% reduction in coronary heart disease for every 1% increase in HDL in the general population.

Using HDL from healthy controls (“healthy HDL”) and from patients with different stages of CKD, Dr. Speer and coworkers incubated isolated aortic endothelial cells with HDL and measured NO production, which increased by about 10% in the presence of healthy HDL but decreased by about 40% in the presence of HDL from stage 5 CKD patients compared with buffer-treated controls. HDL from stage 2 or stage 3/4 patients were associated with the same level of inhibition. Investigators observed a dose-dependent effect, with higher amounts of healthy HDL cholesterol producing greater increases in NO production, and more stage 5 CKD HDL causing more inhibition.

In a study of the mechanism of these effects, the investigators found that HDL in CKD patients increased phosphorylation of an inhibitory site on the endothelial nitric oxide synthase enzyme and decreased phosphorylation of stimulatory sites. HDL from healthy individuals up-regulated phosphorylation of stimulatory sites.

The investigators then looked at the expression of vascular cell adhesion molecule-1 (VCAM-1), which decreased when endothelial cells were incubated in the presence of healthy HDL and the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). However, CKD HDL was associated with a rise in VCAM-1 expression with or without TNF-alpha, and Dr. Speer concluded that HDL cholesterol from end-stage renal disease patients becomes a pro-inflammatory particle.

He also found that HDL from healthy volunteers decreased apoptosis of endothelial cells but that HDL from dialysis patients had no effect, both in vitro and in vivo. In a mouse model of experimental carotid artery injury, whereby mice were injected with HDL and tissue examined three days later, the injured area of endothelium was almost 40% healed in the presence of healthy HDL. HDL from stage 2, 3/4, or 5 CKD patients, however, resulted in much more limited re-endothelialization in a stage-specific manner, e.g., less than 5% of the area was healed in the presence of stage 5 HDL.

Audience member Charlie Tomson, MD, a consultant nephrologist at the North Bristol NHS Trust in  Bristol, United Kingdom and past president of the UK Renal Registry, commented to Renal & Urology News, “It's a fairly convincing set of experiments to me that HDL taken from kidney patients does different things to the endothelium ... compared to HDL from normal patients. It certainly would be an intriguing explanation of why there are such high vascular risks” among patients with CKD. He suggested that it may be informative to conduct epidemiologic studies on CKD patients with different levels of HDL to ascertain if it is vasoprotective or not in real life.

Share this article:
You must be a registered member of RUN to post a comment.
close

Next Article in ERA-EDTA Congress

Sign Up for Free e-newsletters

More in ERA-EDTA Congress

Poor Dental Health Boosts Mortality Risk in ESRD

Poor Dental Health Boosts Mortality Risk in ESRD

In a study, hemodialysis patients with more than 14 decayed, missing, or filled teeth had a 67% increased risk of death.

Pre-Op Physical Status Predicts Surgical Patients' AKI Risk

Pre-Op Physical Status Predicts Surgical Patients' AKI Risk

Increasing ASA scores are associated with an increasing likelihood of post-operative acute kidney injury.

Novel Fluid Protocol Cuts Contrast-Induced AKI Risk

Novel Fluid Protocol Cuts Contrast-Induced AKI Risk

Use of the protocol, which is based on left ventricular end-diastolic pressure, was associated with a 59% relative risk reduction.