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Abstract: FR-OR036

Sevelamer Therapy Associates with a Disturbed Microbial Metabolism in Patients with ESRD

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Dai, Lu, Karolinska Institutet, Stockholm, Sweden
  • Meijers, Björn Ki, UZ Leuven, Leuven, Belgium
  • Bammens, Bert, University Hospitals Leuven, Leuven, Belgium
  • De loor, Henriette, KULeuven, Leuven, Belgium
  • Qureshi, Abdul Rashid Tony, Karolinska Institutet, Stockholm, Sweden
  • Stenvinkel, Peter, Karolinska Institutet, Stockholm, Sweden
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
Background

Sevelamer is a commonly used phosphate binder (PB) in patients(pts) with ESRD. Gastrointestinal discomfort and constipation are frequently reported by sevelamer users, which raises the hypothesis that sevelamer may disturb microbial metabolism. Here we investigate if sevelamer therapy is associated with microbial metabolism in ESRD pts.

Methods

We analyzed serum levels of indoxyl sulphate (IndS) and trimethylamine-N-oxide (TMAO) (as important representatives of colonic microbial metabolism) in a large cohort of ESRD pts (n=423, 65% males, median age 54 years) listed for renal transplantation in Leuven (Belgium, n=347) or Stockholm (Sweden, n=76). Since gut microbial metabolism besides nutritional intake is an important source of VitK, we measured desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP) levels, as a proxy of VitK status. Pts treated either with non-calcium containing PB other than sevelamer or VitK antagonist were excluded. Relevant demographics and biochemistry data were extracted from electronic files. Descriptive and multivariate linear regression analyses were performed to define the role of sevelamer therapy.

Results

Compared with sevelamer non-users, pts treated with sevelamer were characterized with younger age, higher BMI, worse phosphate control, lower albumin, higher serum creatinine, higher serum IndS, TMAO and higher dp-ucMGP levels. In multivariate regression models adjusted for age, gender, phosphate control, serum calcium, calcium containing PB users, dialysis vintage and cohort, sevelamer therapy was identified as an independent determinant of IndS (Odds ratio, [OR 1.41; 95% confidence interval [95%CI], 1.15 to 1.71] and dp-ucMGP (OR[95%CI], 1.46 [1.17 to 1.83]), but not TMAO (1.19 [0.97 to 1.47]). A further adjustment of dp-ucMGP showed that dp-ucMGP is associated with IndS (1.32 [1.19 to 1.46]) and TMAO (1.20 [1.08 to 1.33]).

Conclusion

Sevelamer therapy associates with poor VitK status and an unfavorable microbial metabolism pattern, characterized by high IndS levels. Though the design of our study precludes causal inference, present findings point to a disturbed gut microbial metabolism and VitK deficiency as potential trade-offs of sevelamer therapy and should be considered a call for caution.

Funding

  • Government Support - Non-U.S.