Patients with chronic kidney disease (CKD) have a higher frequency of cardiovascular disease and mortality. A study published in the American Journal of Nephrology, called IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD), investigated the association between CKD and cardiovascular disease (CVD) and its relation to elevated phosphate levels in the blood (hyperphosphatemia), which stem from weak kidney function.*

Background information

Healthy kidneys filter the blood—removing wastes and extra water from the body to convert them into urine. The kidneys’ primary function is to maintain a healthy balance of water, salts, and minerals, including phosphorus, calcium, sodium, and potassium. Healthy kidneys also produce hormones (erythropoietin, calcitriol, and renin) that help to control blood pressure and keep bones strong.

A decline in kidney function leads to a disruption of salts and minerals balance in the blood. When this balance is disturbed, the function of other organs and tissues in the human body can worsen. From stage 3 of CKD onwards, the kidneys’ ability to properly excrete phosphate is diminished, leading to an accumulation of phosphate in the blood (hyperphosphatemia). Disturbances in kidney function also cause abnormalities in the blood’s levels of calcium, hormones, and vitamins, such as vitamin D. 

Research and investigation details

Researchers and physicians performed “an international, multi-centre, randomized, placebo-controlled trial” to investigate the effects of lanthanum carbonate, a phosphate binder, on cardiac biomarkers in CKD patients between stages 3b and 4. Of 278 CKD participants, 33% were stage 3b patients, and 67% were stage 4 patients. Some participants received lanthanum carbonate, while others were given a placebo (an inert substance designed to have no therapeutic value). 

There were two measurable end-points—change in carotid-femoral pulse wave velocity (PWV) and change in abdominal aortic calcification (AAC), serum phosphate, and fibroblast growth factor 23. What this means is that vascular calcifications and levels of phosphate, hormones, and vitamins in the blood were measured. Measurements were taken after 96 weeks.

Results and conclusions

The clinical trial concluded that there is a link between AAC and a series of identified factors, which include:

• older age;
• male gender; 
• diabetes;
• CVD;
• higher diastolic BP; 
• dyslipidemia (and use of statins); 
• smoking; 
• larger waist circumference; and 
• raised PWV.

Based on their findings, the study also confirmed that CKD patients have a higher level of risk for cardiovascular disease and/or events, due to higher PWV and AAC values.

Further reading can be found on MDLinx in their summary of the above trial.

*Lioufas, N., Pedagogos, E., Hawley, C., Pascoe, E., et al. (2020, Feb. 5). “Aortic Calcification and Arterial Stiffness Burden in a Chronic Kidney Disease Cohort With High Cardiovascular Risk: Baseline Characteristics of the Impact of Phosphate Reduction On Vascular End-Points in Chronic Kidney Disease Trial.” American Journal of Nephrology.