Effect of Lanthanum Carbonate on Serum Phosphate, Oxidative Stress, and Vascular Dysfunction in CKD: A Mechanistic Randomized Controlled Trial

Key Points:

1. A key mechanism contributing to vascular dysfunction in CKD is increased oxidative stress.

2. Lanthanum carbonate did not discernibly affect vascular endothelial function, arterial stiffness, or markers of endothelial oxidative stress.

Background: Vascular endothelial dysfunction and arterial stiffness are common in CKD and independently predict cardiovascular disease. Elevated serum phosphorus, even within the normal range, associates with cardiovascular disease and mortality in CKD. Excess phosphorus may increase oxidative stress leading to vascular dysfunction.

Methods: This is a randomized double-blind trial in which we compared lanthanum carbonate, a noncalcium phosphate binder, with placebo on vascular function and endothelial and circulating measures of oxidative stress and inflammation in 54 participants with CKD 3b–4 and normal phosphorus levels. Primary end points were change in brachial artery flow-mediated dilation (FMD_BA) and carotid-to-femoral pulse-wave velocity (cfPWV) at 12 weeks. Mechanistic end points were changes from baseline in FMD_BA after ascorbic acid infusion and circulating and endothelial markers of oxidative stress and inflammation.

Results: The age was 65±8 years and eGFR was 38±14 ml/min per 1.73 m². At 12 weeks, serum phosphorus did not change with lanthanum (3.44±0.47 versus 3.44±0.52 mg/dl; P = 0.94) but tended to increase with placebo (3.42±0.80 versus 3.74±1.26 mg/dl; P = 0.09). FMD_BA and cfPWV did not change from baseline in either group: FMD_BA lanthanum 3.13%±2.87% to 2.73%±2.48% versus placebo 3.74%±2.86% to 3.09%±2.49% (P = 0.67); CfPWV lanthanum 1214±394 to 1216±322 cm/s versus placebo 993±289 to 977±254 cm/s (P = 0.77). Ascorbic acid infusion to inhibit oxidative stress did not differentially affect FMD_BA. Circulating and endothelial markers of oxidative stress and inflammation did not differ between groups.

Conclusions: Lanthanum carbonate did not discernibly affect vascular endothelial function, arterial stiffness, or markers of endothelial oxidative stress among participants with CKD 3b–4 and normophosphatemia.