Kidney Week

Abstract: FR-OR040

Phosphate Lowering to Treat Vascular Dysfunction in CKD

Session Information

• Bone and Mineral Metabolism: Clinical Research
  November 08, 2019 | Location: 145, Walter E. Washington Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Jovanovich, Anna Jeanette, Denver VA / University of Colorado, Denver, Colorado, United States

Anna Jeanette Jovanovich, MD

• You, Zhiying, UC Denver, Aurora, Colorado, United States

Zhiying You,

• Struemph, Taylor, University of Colorado, Denver, Aurora, Colorado, United States

Taylor Struemph,

• Farmer, Beverly, University of Colorado , Aurora, Colorado, United States

Beverly Farmer,

• Malaczewski, Mikaela R., No, Aurora, Colorado, United States

Mikaela R. Malaczewski,

• Levi, Moshe, Georgetown University, Washington, District of Columbia, United States

Moshe Levi,

• Schwartz, Gregory G., Rocky Mtn Regional VA Med Ctr and University of Colorado School of Medicine, Aurora, Colorado, United States

Gregory G. Schwartz,

• Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States

Kristen L. Nowak,

• Chonchol, Michel, University of Colorado , Aurora, Colorado, United States

Michel Chonchol,

Background

Individuals with CKD exhibit vascular endothelial dysfunction and arterial stiffness, independent predictors of cardiovascular disease (CVD) events. Elevated serum phosphorus, even within the normal range, is associated with CVD and mortality in CKD. An acute increase in serum phosphorus impairs endothelial function and increases vascular oxidative stress. We hypothesized that lowering serum phosphorus would improve vascular function and endothelial markers of oxidative stress in CKD.

Methods

We randomized 52 participants with CKD 3b-4 and serum phosphorus within normal limits to receive 12 weeks of lanthanum carbonate or placebo. Primary endpoints were change in brachial artery flow-mediated dilation (FMD_BA) and aortic pulse-wave velocity (aPWV). Secondary endpoints were change in FMD_BAand aPWV after ascorbic acid infusion and vascular endothelial cell protein expression of NADPH oxidase and NFκB.

Results

Mean age was 65±8 years and mean eGFR was 38±14 mL/min/1.73m². Baseline serum phosphorus (3.44±0.47 mg/dL) in the lanthanum carbonate group did not change after 12 weeks (p=0.94) while serum phosphorus increased (3.42±0.80 mg/dL to 3.74±1.26 mg/dL; p = 0.09) after 12 weeks in the placebo group. Randomization to lanthanum carbonate did not improve FMD_BAor aPWV compared to placebo: lanthanum carbonate baseline FMD_BA 3.13%±2.87% and 12-week FMD_BA 2.73%±2.48% vs. placebo baseline FMD_BA 3.74%±2.86% and 12-week FMD_BA 3.09%±2.49%; p=0.52; and lanthanum carbonate baseline aPWV 1214±394 cm/sec and 12-week aPWV 1216±322 cm/sec vs. placebo baseline aPWV 993±289 cm/sec and 12-week aPWV 977±254 cm/sec; p=0.66. Supraphysiologic infusion of ascorbic acid to inhibit superoxide production did not differentially change FMD_BA or aPWV between groups at the end of the study (p>0.1 for all). Vascular endothelial cell protein expression of NADPH oxidase and NFκB did not change in either group (p>0.6 for all groups).

Conclusion

Compared to placebo, lanthanum carbonate did not improve vascular endothelial function or stiffness nor did it change endothelial markers of oxidative stress among participants with CKD 3b-4. Infusion of ascorbic acid to inhibit oxidative stress did not differentially affect FMD_BA or aPWV.

Funding

• Veterans Affairs Support