Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis
Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis:
A pilot randomized controlled trial
Toussaint N et al
cited from: Nephrology 16 (2011) 290–298
Chronic kidney disease (CKD) is a potent independent risk factor for cardiovascular disease (CVD).1 Non-traditional risk factors such as vascular calcification (VC) contribute to the significantly increased rates of cardiovascular events and mortality in CKD.2,3 A mediated complex of factors is involved in the pathogenesis of VC, with precipitation of VC by abnormal mineral metabolism, including calcium and phosphate excess, as well as uraemia. Reflecting an increased recognition of the close relationship of mineral metabolism to VC, bone abnormalities and consequences of fracture, CVD and increased mortality, the term ‘CKD-Mineral and Bone Disorder’ (CKD-MBD) was recently introduced to encompass these abnormalities.4
Phosphate is arguably the most important biochemical parameter of CKD-MBD and an important inducer of VC. Serum levels of phosphate are linearly and independently associated with all-cause and cardiovascular mortality in CKD patients on dialysis5,6 and the use of phosphate binders has been associated with improved survival in this population. 7 Calcium-based binders are inexpensive, effective and most widely used, but there is increasing concern about their association with hypercalcaemia and VC. A greater calciumphosphate product (Ca ¥ P) and the dosage of oral calcium ingested, predominantly through administration of calciumbased phosphate binders, have been significantly associated with the likelihood of developing VC.8,9 Several studies including randomized controlled trials in prevalent and incident haemodialysis (HD) patients, demonstrate reduced progression of VC, both of the coronary arteries and aorta, in patients taking the non-calcium-based phosphate binder sevelamer hydrochloride compared with calcium-containing binders.10,11 Lanthanum carbonate (LC) is another newer phosphate binder that does not contain aluminium or calcium. Lanthanum is a naturally occurring element that has a similar phosphate-binding capacity to aluminium, but, unlike aluminium, is minimally absorbed.12 LC is as effective as calcium-based binders but may potentially lead to improvements in bone health and reduction of VC with reduction in exogenous calcium.13,14 Treatment with LC is not associated with hypercalcaemia and studies have confirmed the safety and efficacy of up to 6 years of treatment.15,16 LC has also been compared with sevelamer hydrochloride in a randomized study in a dialysis population showing similar achievement of serum phosphate levels.17 Experimental studies assessing lanthanum suggest a benefit on reducing VC18–20 but there is limited clinical data on the effect of this agent on VC in CKD. The main aim of this study was to evaluate the effects of LC compared with calcium-based phosphate binders on VC in HD patients in a pilot randomized controlled trial.
Vascular calcification (VC) contributes to cardiovascular disease in haemodialysis (HD) patients. Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial. No published randomized study to date has assessed the effect of lanthanum carbonate (LC) on VC progression.
We conducted a pilot randomized controlled trial to determine the effect of LC on VC. Forty-five HD patients were randomized to either LC or calcium carbonate (CC). Primary outcome was change in aortic VC after 18 months. Secondary outcomes included superficial femoral artery (SFA) VC, bone mineral density (BMD) of lumbar spine and serum markers of
mineral metabolism. At baseline, 6 and 18 month computed tomography was performed to measure VC and BMD. A random effect linear regression model was performed to assess differences.
Thirty patients completed the study (17 LC, 13 CC); baseline median age 58 years, 38% diabetic, 64% male. Ninety-three per cent had aortic VC at commencement and 87% showed progression. At 18 months, there was significantly less aortic VC progression with LC than CC (adjusted difference -98.1 (-149.4, -46.8) Hounsfield units (HU), P < 0.001). There was also a nonsignificant reduction with LC in left SFA VC (-25.8 (-67.7, 16.1) HU, P = 0.2) and right SFA VC (-35.9 (-77.8, 5.9) HU, P = 0.09). There was no difference in lumbar spine BMD and serum phosphate, calcium and parathyroid hormone levels between groups. Limitations to the study include small sample size and loss to follow up.
Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months.