#6124 INTERACTIONS BETWEEN FIBROBLAST GROWTH FACTOR 23 AND SYSTEMIC INFLAMMATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Background and Aims In patients with Chronic Kidney Disease (CKD), serum concentration of Fibroblast Growth Factor 23 (FGF23) is inversely correlated with Glomerular Filtration Rate (eGFR), as an adaptive mechanism to counterbalance the alterations of mineral metabolism. Transcription, secretion and cleavage from the intact form (iFGF23) to the c-terminal fraction (cFGF23) are regulated by several mechanisms among which inflammatory mediators seem to play a significant role. We investigated whether there was any correlation between FGF23 and several inflammatory mediators. Method In the present study we evaluated cross sectionally the correlation between FGF23 (iFGF23 and c-FGF23) and some pro-inflammatory (IL-6, TNFα, MCP-1)) and anti-inflammatory (IL-10) cytokines in a cohort of 111 prevalent CKD patients stages III-V not yet on dialysis. We excluded patients with infections or chronic inflammatory diseases in the last 3 months, neoplasia or under immunosuppressive therapy. FGF23 and cytokines were dosed by ELISA. Results Descriptive characteristics of the cohort are reported in Table 1. We found an increase in inflammation as eGFR declines: IL6 (r = -0,315, p<0,001), TNFa (r = -0,202, p = 0,033) and MCP1 (r = -0,278, p = 0,003). Furthermore, the ratio between C-terminal FGF23 to intact FGF23 (c/iFGF23) was directly related to eGFR, even if it did not reach statistical significance (r = 0,127, p = 0,113). The correlations between FGF23 and markers of osteo-mineral metabolism and inflammation are reported in Table 2. We found positive correlations of iFGF23 with: IL-6 (r = 0,465, p<0,001), TNFα (r = 0,241, p = 0,009) and IL-10 (r = 0,198, p = 0,044) Conversely, cFGF23 only correlated with MCP-1 (r = 0,264, p = 0,005). c/iFGF23 resulted inversely correlated with IL-6 (-0,326, p<0,001) and positively with MCP-1 (r = 0,178, p = 0,061). After the adjustment for eGFR, iFGF23 maintained his correlations only with IL-6 (r = 0,370, p < 0,001) and TNFα (r = 0,163, p = 0,044) while c/iFGF23 was negatively correlated with IL-6 (r -0,251, p = 0,008) and positively with MCP-1 (r = 0,204, p = 0,032). Conclusion Our data confirm that in CKD patients, as the renal function declines, there is an important increase of inflammatory cytokines and a tendency to an impaired cleavage of FGF23 from the intact to the c-terminal form. Furthermore, we observed strong correlations of iFGF23 with several inflammatory cytokines (IL-6, TNFα, IL-10) that seem to be independent of eGFR. On the contrary we did not find any correlation of cFGF23 with inflammatory mediators, except for MCP-1. Therefore, we believe that overall our results suggest that inflammatory markers are differently associated with cFGF23 and iFGF23, as if inflammation may independently influence FGF23 turnover (i.e, c/iFGF23 ratio).