No Cardiovascular Benefit from Phosphate Binders in Chronic Kidney Disease Patients

Nigel D. Toussaint, MBBS, FRACP, PhD

There might not be a cardiovascular benefit for chronic kidney disease (CKD) patients prescribed phosphate binders, according to new research.

An international team, led by Nigel D. Toussaint, MBBS, FRACP, PhD, Department of Nephrology, The Royal Melbourne Hospital, assessed the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers in patients suffering from chronic kidney disease.

For patients with chronic kidney disease, higher serum phosphate levels is linked to increased fibroblast growth factor 23 (FGF23) levels, arterial calcification, and cardiovascular mortality. However, there has only been limited trial assessing phosphate-lowering therapies, with only modest efficacy in lowering serum phosphate and FGF23 found during short-term follow-up with patients.

While phosphate binders like lanthanum have been prescribed to help reduce the risk of bone and cardiovascular disease, the effect of these agents on cardiovascular markers is uncertain.

In the multicenter, double-blind, randomized trial, the investigators examined 278 patients with stage 3b or 4 chronic kidney disease and serum phosphate greater than 1.00 mmol/L (3.10 mg/dl). Each patient received either 500 mg of lanthanum carbonate (n = 138) or a matched placebo (n = 140) 3 times daily for 96 weeks.

The mean age of the study was 63.1 years old and the patient population was 69% male. The mean estimated glomerular filtration rate (eGFR) of 26.6 ml/min per 1.73 m2 and 45% and 32% of participants had diabetes and cardiovascular disease, respectively.

The mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), the mean pulse wave velocity was 10.8 m/s, and 81.3% of the study population had abdominal aortic calcification at baseline.

The investigators sought a primary outcome of carotid-femoral pulse wave velocity, which was analyzed using a linear mixed effects model for repeated measures. They also sough secondary outcomes of abdominal aortic calcification and serum and urine markers of mineral metabolism.

After 96 weeks, the investigators found pulse wave velocity did not significantly differ between the treatment and placebo group. Abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate also did not differ between the treatment group and placebo group at 96 weeks.

Serious adverse events also occurred in 63 (46%) of patients in the lanthanum group and 66 (47%) individuals in the placebo group.

While the recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.

“In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo,” the authors wrote. “These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.”

The study represents the largest trial to look at the impact of lanthanum carbonate in patients with chronic kidney disease.

The study, “A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD),” was published online in the Journal of the American Society of Nephrology.