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Abstract: FR-PO225

Elevated Serum Osteoprotegerin Associates with Microbiota-Derived Phenylacetylglutamine and Vascular Calcification in CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Dai, Lu, Karolinska Institutet, Stockholm, Sweden
  • Qureshi, Abdul Rashid Tony, Karolinska Institutet, Stockholm, Sweden
  • Lindholm, Bengt, Karolinska Institutet, Stockholm, Sweden
  • Heimburger, Olof, Karolinska Institutet, Stockholm, Sweden
  • Barany, Peter F., Karolinska Institutet, Stockholm, Sweden
  • Soderberg, Magnus, AstraZeneca, Molndal, Sweden
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
  • Stenvinkel, Peter, Karolinska Institutet, Stockholm, Sweden
Background

Increasing evidence indicate that a complex interplay between reduced renal function, altered bone metabolism and increased levels of metabolites produced by the gut microbiota drives vascular calcification (VC) which causes considerable morbidity and mortality in patients with chronic kidney disease (CKD). Here we investigated if osteoprotegerin (OPG), an osteocyte-derived inhibitor of bone formation, is associated with phenylacetylglutamine (PAG), a gut microbial metabolite, and VC in CKD stage 5 patients.

Methods

In 112 living donor kidney transplant (LD-Rtx) recipients (63% males; median age 47 years), associations between severity of VC (score 0 to 3; evaluated by histological examination of epigastric artery specimens collected at LD-Rtx), and serum OPG and PAG were investigated. Patients with VC grade 0 (n=17) and 1 (n=51) were combined into Group 1, representing no or minimal VC (n=68), and those having moderate (score 2; n= 29) or extensive (score 3; n= 15) VC were combined into Group 2 (n=44).

Results

Group 2 patients had significantly higher OPG levels than Group 1 patients with no or minimal VC. In Spearman’s rank correlations, OPG was positively associated with age, bone specific alkaline phosphatase, PAG, high-sensitive C-reactive protein and percentage calcification. Multivariate regression analyses showed that after adjustments for age, sex, diabetes and smoking habits, 1-SD higher level of PAG (β=0.35 P<0.001) was independently associated with 1-SD higher OPG level (adjusted r2=0.44). OPG was significantly associated with VC score after adjustments for age, sex, diabetes, smoking habits and PAG (OR [95% CI]: 2.05 [1.08, 3.89]; p=0.03).

Conclusion

While gut microbiome assessed by PAG is closely related with bone metabolism as assessed by OPG in CKD patients, serum OPG is a strong predictor of biopsy-verified VC, independent of gut microbiota status as assessed by PAG.