N M LIOUFAS1,2,3, S SM CHEN4,5, C M HAWLEY6,7, E PEDAGOGOS2,3, E M PASCOE6, A VALKS6, N D TOUSSAINT1,2
1Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine (RMH), The University of Melbourne, Parkville, Australia, 3Western Health, St Albans, Australia, 4Epworth Healthcare, Melbourne, Australia, 5The Prince Charles Hospital, Brisbane, Australia, 6Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia, 7Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
Aim: To evaluate the effects of phosphate-lowering therapy on cardiac structure and function, determined by cardiovascular magnetic resonance (CMR), in patients with chronic kidney disease (CKD).
Background: CKD and abnormalities in mineral metabolism are associated with increased cardiovascular disease (CVD), including changes in cardiac structure and function. Increased levels of fibroblast growth factor-23 (FGF23) may contribute to uraemic cardiomyopathy, with associated changes in left ventricular mass. Decreasing intestinal phosphate absorption may mitigate increased FGF23 and reduce cardiovascular complications.
Methods: IMPROVE-CKD was a multi-centre, placebo-controlled, randomised trial assessing effects of the phosphate binder lanthanum carbonate on cardiovascular markers over 96 weeks in 278 participants with CKD stages 3b/4. Primary outcome was carotid-femoral pulse wave velocity (cfPWV, SphygmoCor), and secondary outcomes included abdominal aortic calcification (AAC). In a CMR sub-study, cardiac parameters including left ventricular mass index (LVMI), ascending aortic distensibility (AAD) and aortic PWV were evaluated by CMR at baseline and 96 weeks.
Results: 62 participants completed the CMR sub-study (placebo 33; lanthanum 29). Mean age was 59.9±13.5yrs, 63% male, 55% Caucasian, mean BMI 28.7±4.6kg/m² and mean eGFR 27.5±9.0ml/min/1.73m². 39% had diabetes, 82% hypertension, and 19% CVD. At 96 weeks, there were no significant differences in cfPWV, AAC, serum phosphate and FGF23 between treatment groups. There were also no significant differences in LVMI, left atrial dilation, left ventricular ejection fraction or AAD between groups, however there was a difference in aortic PWV favouring lanthanum (mean change -3.14±8.7 vs 1.27±3.15m/s, p=0.048).
Conclusions: In patients with CKD3b/4, treatment with lanthanum carbonate over 96 weeks did not affect arterial stiffness, aortic calcification or cardiac parameters compared with placebo. Reduced change in aortic PWV seen with lanthanum needs further evaluation.
Dr Nicole Lioufas is a Research Fellow at the Royal Melbourne Hospital and works a Nephrologist and General Medical Consultant at Western Health. She is currently undertaking a PhD through the University of Melbourne in the role of phosphate binders on vascular calcification and cardiovascular outcomes in chronic kidney disease.