Background: Higher serum intact fibroblast growth factor 23 (iFGF23) was associated with disease progression in participants with autosomal dominant polycystic kidney disease (ADPKD) in the HALT-PKD Studies. PKD mutation is also an important determinant of progression. We hypothesized that serum levels of iFGF23 and vitamin D metabolites (1,25-dihydroxyvitamin D [1,25(OH)D] and 25-hydroxyvitamin D [25[OH]D]) differ according to ADPKD mutation and differentially predict clinical end points according to genotype (significant interaction between genotype and mineral metabolites).
Methods: A total of 864 individuals with ADPKD who participated in the HALT-PKD Study A or B and had measurements of mineral metabolites (1,25[OH]D, 25[OH]D, iFGF23) were categorized by PKD mutation (PKD1 truncating, PKD1 nontruncating, PKD2, or no mutation detected [NMD]). The association of the interactions of genotype × iFGF23, genotype × 1,25(OH)2D, and genotype × 25(OH)D with () annualized change in eGFR; () mean annualized percentage change in height-corrected total kidney volume (Study A only); and () time to a composite of 50% reduction in eGFR, ESKD, or death were evaluated using linear regression and Cox proportional hazards regression.
Results: Median (interquartile range) iFGF23 differed (PKD1 truncating, 55.8 [40.7-76.8]; PKD1 nontruncating, 49.9 [37.7-71.0]; PKD2, 49.0 [33.8-70.5]; NMD, 50.3 [39.7-67.4] pg/ml; =0.03) and mean±SD 1,25(OH)D differed (PKD1 truncating, 32.8±12.8; PKD1 nontruncating, 33.4±12.5; PKD2, 34.1±13.1; NMD, 38.0±14.6 pg/ml; =0.02) according to PKD genotype. There was a significant interaction between iFGF23 and genotype (=0.02) for the composite end point in fully adjusted models, but no significant interaction between 1,25(OH)D or 25(OH)D and genotype for clinical end points.
Conclusions: ADPKD genotype interacts significantly with FGF23 to influence clinical end points. Whereas the worst outcomes were in individuals with a PKD1-truncating or -nontruncating mutation and the highest iFGF23 tertile, risk of the composite end point differed according to iFGF23 the most in the PKD1-nontruncating and PKD2 groups.
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| http://dx.doi.org/10.34067/KID.0001692020 | DOI Listing |
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