M TIONG1,2, ER SMITH1,2, NM LIOUFAS1,2,3, E PEDAGOGOS3, EM PASCOE4, CM HAWLEY4,5, A VALKS4, ND TOUSSAINT1,2
1Department of Nephrology – The Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine (RMH) – University of Melbourne, Parkville, Australia, 3Department of Nephrology – Western Health, Sunshine, Australia, 4Australasian Kidney Trials Network – The University of Queensland, Brisbane, Australia, 5Department of Nephrology – Princess Alexandra Hospital, Brisbane, Australia
Aim: To examine the effect of lanthanum carbonate compared to placebo on calciprotein particles (CPPs) in patients with chronic kidney disease (CKD).
Background: Patients with CKD are at increased risk of hyperphosphataemia and accelerated cardiovascular calcification and death. Mechanisms linking these events are yet to be completely defined. CPPs are endogenous, nanoscale, colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of phosphate toxicity. Long-term effects of phosphate binders on CPPs is unknown.
Methods: IMPROVE-CKD was a multi-centre, placebo-controlled, randomised trial assessing effects of the phosphate binder lanthanum carbonate on cardiovascular markers over 96weeks in 278 participants with CKD stages 3b/4. Primary outcome was pulse wave velocity, and secondary outcomes included aortic calcification. Amorphous calcium phosphate containing (CPP-1) and hydroxyapatite containing (CPP-2) calciprotein particles were measured by flow cytometry in a sub-cohort of participants at baseline and 96weeks. Treatment groups were compared on change scores of CPPs using non-parametric Wilcoxon rank-sum test.
Results: 133 participants had complete CPP measurements (placebo 56; lanthanum 77). Mean age 62.7±12.5yrs, eGFR 26.8±8.5ml/min/1.73m2, 68% male, 41% diabetic, 27% cardiovascular disease. Mean serum phosphate was 1.24±0.19mmol/L, serum calcium 2.33±0.14mmol/L, median PTH 12.9[6.7–18.3]pmol/L and c-terminal FGF23 227[145–349]RU/mL. Baseline median CPP-1 was 9.5[3.4–29.4]x10^5/ml and CPP-2 2.4[1.0–4.4] x10^3/ml, with no significant difference in levels over 96weeks in the overall group. There was also no significant difference between treatment groups at 96weeks in CPP-1 (median change 2.2[-1.0–2.5]x10^5/ml vs 1.4[-1.6–2.2] x10^5/ml, p=0.54), or in CPP-2 (1.1[-10.1–10.6]x10^3/ml vs -2.5[-25.2–26.1]x10^3/ml, p=0.70) for lanthanum carbonate vs placebo respectively.
Conclusions: Lanthanum carbonate was not associated with a reduction of CPPs at 96 weeks when compared to placebo.
Dr Mark Tiong completed his RACP fellowship in nephrology in 2019 and is currently undertaking his PhD in the area of CKD-MBD at The Royal Melbourne Hospital and The University of Melbourne. He is also interested in Aboriginal and Torres Strait Islander health, having previously worked for the Central Australian Health Service in Alice Springs, and is also a current member of the ANZDATA Aboriginal and Torres Strait Islander Health Working Group.