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Abstract: TH-PO270

Iron Rather than Erythropoietin Mediates the Role of Fibroblast Growth Factor 23 in Renal Anemia in Humans

Session Information

Category: Anemia and Iron Metabolism

  • 201 Anemia and Iron Metabolism: Basic

Authors

  • Bielesz, Bernhard O., Medical University of Vienna , Vienna, w, Austria
  • Hammerle, Fabian Peter, Medical University of Vienna , Vienna, w, Austria
  • Reiter, Thomas Johannes, Medical University of Vienna , Vienna, w, Austria
  • Bojic, Marija, Medical University of Vienna , Vienna, w, Austria
  • Gleiss, Andreas, Medical University of Vienna , Vienna, w, Austria
  • Marculescu, Rodrig, Medical University of Vienna , Vienna, w, Austria
Background

Renal anemia is an almost universal complication of chronic kidney disease (CKD). In animal experiments,Fibroblast growth factor 23 (FGF23),a well-known key-player in mineral metabolism,has been causally implicated by suppressing erythropoietin (EPO). We assessed whether FGF23 might contribute to anemia by inducing relative EPO deficiency.

Methods

Hemoglobin,EPO,iron,and mineral metabolism parameters,including both intact (Diasorin) and c-terminal (Immutopics) FGF23 were measured in 225 non-dialysis CKD (stage 1-5,median eGFR 30 ml/min/1.75m2) patients not on erythrocyte stimulating agent or intravenous iron therapy. To approximate relative EPO deficiency, EPO values from 5483 patients collected at the General Hospital of Vienna with CRP<1 mg/dl and GFR>60 (median eGFR 87) were chosen as reference population for modelling of gender-specific EPO-standard deviation scores (EPO-SDS) stratified to corresponding hemoglobin levels. Analysis was performed by multiple linear regression.

Results

Both intact and c-terminal FGF23 were associated with hemoglobin in univariate analysis but only cFGF23 remained significant after adjustment. Inclusion of EPO-SDS did not alter the association of cFGF23 with hemoglobin. In contrast, iron indices largely displace this interaction.

Conclusion

In patients with predominantly moderate to severe renal function impairment,relative EPO deficiency fails to explain the association of cFGF23 with anemia,which rather seems to be mediated by iron metabolism.

Table 2
 Base modelIron modelEPO modelInflammation model
MarkerBeta95% CI limitspBeta95% CI limitspR2Beta95% CI limitspR2Beta95% CI limitspR2
cFGF23 (RU/ml)*-0.28-0.44/-0.110.001-0.15-0.34/0.040.1260.51-0.32-0.47/-0.17<0.0010.58-0.28-0.45/-0.110.0010.49
phosphate (mmol/l)*-0.75-1.42/-0.070.032-0.76-1.51/-0.020.0450.51-0.12-0.79/0.540.7120.54-0.76-1.45/-0.060.0330.46
total calcium (mmol/l)2.150.91/3.39<0.0011.950.65/3.240.0030.531.350.17/2.540.0260.552.110.86/3.370.0010.48

Dependent variable:Hemoglobin;Base model:eGFR,gender,albumin,DM II;Iron model:Base PLUS serum iron,hepcidin,transferrin saturation,ferritin,transferrin;EPO model:Base PLUS EPO-SDS;Inflammation model:Base PLUS CRP,interleukin 6

Table 1