Kidney Week

Abstract: TH-PO186

Interactions Between FGF23 and Genotype in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

• Bone and Mineral Metabolism: Clinical - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Grau, Laura K., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States

Laura K. Grau,

• Gitomer, Berenice Y., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States

Berenice Y. Gitomer,

• Chonchol, Michel, University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States

Michel Chonchol,

• Wolf, Myles, Duke University, Durham, North Carolina, United States

Myles Wolf,

• Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States

Peter C. Harris,

• Brosnahan, Godela M., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States

Godela M. Brosnahan,

• Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States

Vicente E. Torres,

• Steinman, Theodore I., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Theodore I. Steinman,

• Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States

Alan S.L. Yu,

• Chapman, Arlene B., University of Chicago, Chicago, Illinois, United States

Arlene B. Chapman,

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

Kristen L. Nowak,

Background

Among individuals with ADPKD, higher serum intact fibroblast growth factor 23 (iFGF23) was associated with disease progression in participants in the HALT-PKD study. PKD mutation is also an important determinant of ADPKD progression. We hypothesized that serum levels of iFGF23 and vitamin D metabolites (1,25-dihydroxyvitamin D [1,25(OH)₂D] and 25-hydroxyvitamin D [25[OH]D]) differed in adults with ADPKD according to ADPKD mutation and that the interaction between genotype and mineral metabolites would predict clinical endpoints.

Methods

921 individuals with ADPKD who participated in the HALT-PKD study A or B and had measurement of mineral metabolites (1,25(OH)₂D, 25(OH)D, and iFGF23) were categorized by PKD mutation (PKD1 truncating, PKD1 non-truncating, PKD2, or no mutation detected [NMD]). The longitudinal (5-yr) association of the interactions of genotype * iFGF23 and genotype * 1,25(OH)₂D with clinical endpoints of (a) 50% decline in eGFR; b) end-stage renal disease (ESRD); c) composite of 50% decline in eGFR, ESRD, or death) were evaluated using cox proportional hazards regression.

Results

Median (IQR) 1,25(OH)₂D differed (PKD1 truncating: 31.0 (24.4, 39.1); PKD1 non-truncating: 32.0 (24.8, 40.1), PKD2: 33.9 (24.8,41.0); NMD: 38.2 (27.8, 46.4) pg/ml; p=0.01) and iFGF23 tended to differ (PKD1 truncating: 55.9 (40.5, 76.2); PKD1 non-truncating: 49.9 (37.7, 72.2); PKD2: 48.6 (33.9, 69.8); NMD: 49.8 (39.7, 65.8) pg/ml; p=0.07) according to PKD genotype. There was a significant interaction between FGF23 and genotype (p<0.01) for the composite endpoint in the fully adjusted models (Figure), but no significant interaction between 1,25(OH)₂D and genotype for clinical endpoints.

Conclusion

ADPKD genotype interacts significantly with FGF23 to influence clinical endpoints, with the worst outcomes in individuals with a PKD1 truncating or non-truncating mutation and the highest tertile of iFGF23.

Funding

• NIDDK Support