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Kidney Week

Abstract: TH-PO1190

IMpact of Phosphate Reduction on Vascular End-Points in CKD (IMPROVE-CKD): A Randomized, Placebo-Controlled Trial

Session Information

Category: Bone and Mineral Metabolism

Authors

  • Toussaint, Nigel David, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • Pedagogos, Eugenia, Alfred Health, Melbourne, Victoria, Australia

Group or Team Name

  • IMPROVE-CKD investigators
Background

Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, arterial stiffness and increased cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). Due to these associations, clinical guidelines recommend lowering serum phosphate levels towards the normal range. However, the effect of phosphate-lowering medications on markers of vascular calcification and arterial stiffness in non-dialysis CKD patients remains uncertain. The aim of IMPROVE-CKD was to assess the effects of a non-calcium-based phosphate binder, lanthanum carbonate, on intermediate CV markers in patients with CKD.

Methods

In this double-blind, multi-centre, randomized controlled trial, patients with stage 3b or 4 CKD were randomized to lanthanum carbonate 500mg or matched placebo three times daily for 96 weeks. The primary outcome was change in carotid-femoral pulse wave velocity (PWV, SphygmoCor). Intention-to-treat analysis was used with linear mixed models for repeated measures. Secondary outcomes included aortic calcification (AC, computed tomography), and serum and urine markers of bone and mineral metabolism.

Results

278 participants from Australia, Malaysia and New Zealand were randomized to lanthanum carbonate (n=138) or placebo (n=140) (mean age 63.1±12.7yrs, 69.4% male, 63.9% white; 33% stage 3b CKD, 67% stage 4 CKD, mean eGFR 26.6±8.3ml/min/1.73m2; 45% diabetes, 32.1% CV disease). Mean serum phosphate was 1.25±0.20mmol/L, mean PWV 10.8±3.6m/s and 81.3% had AC at baseline (median [IQR] 1535 [63.2, 5744] Hounsfield Units [HU]). At 96 weeks, change in PWV did not differ significantly between the groups (diff [95%CI] +0.7 [-0.2, 1.6] m/s, p=0.13). Change in AC score was also not significantly different (+154 [-334, 641] HU, p=0.53) and there were no differences in serum phosphate, c-terminal and intact FGF23, and 24-h urinary phosphate excretion between the groups. Serious adverse events were reported in 63 (46%) and 66 (47%) participants on lanthanum and placebo respectively.

Conclusion

In stage 3b/4 CKD patients, treatment with the phosphate-lowering agent lanthanum carbonate over 96 weeks did not result in any difference in change in arterial stiffness or aortic vascular calcification.

Funding

  • Commercial Support