Affiliation:
1. Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
2. Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
3. Renal Research Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
Abstract
Background: In patients with chronic kidney disease (CKD), Fibroblast Growth Factor 23 (FGF23) is markedly increased and has been proposed to interact with systemic inflammation. Methods: In this cross-sectional study, we evaluated the correlations of intact FGF23, c-terminal FGF23, and the FGF23 ratio (c-terminal to intact) with some inflammatory cytokines in 111 elderly patients with advanced CKD not yet in dialysis. Results: Estimated glomerular filtration rate (eGFR) was inversely correlated with intact FGF23 and c-terminal FGF23, as well as with interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP-1). Intact FGF23 levels were directly correlated with IL-6 (r = 0.403; p < 0.001) and TNFα (r = 0.401; p < 0.001) while c-terminal FGF23 was directly correlated with MCP-1 (r = 0.264; p = 0.005). The FGF23 ratio was, instead, inversely correlated with IL-6 (r = −0.326; p < 0.001). Multivariate analysis revealed that intact FGF23 was directly associated with TNFα [B = 0.012 (95% CI 0.006, 0.019); p = 0.003] and c-terminal FGF23 was directly associated with MCP-1 [B = 0.001 (95% CI 0.000, 0.002); p = 0.038], while the FGF23 ratio was inversely correlated with IL-6 [B = −0.028 (95% CI −0.047, −0.010); p = 0.002]. Conclusions: Our data demonstrate that, in CKD patients, intact FGF23 and the metabolites deriving from its proteolytic cleavage are differently associated with some inflammatory pathways. In particular, intact FGF23 is mainly associated with IL-6 and TNFα, c-terminal FGF23 with MCP-1, and the FGF23 ratio with IL6.
Funder
Italian Ministry of Health
Reference44 articles.
1. Epidemiology of chronic kidney disease: An update 2022;Kovesdy;Kidney Int. Suppl.,2022
2. Chronic Kidney Disease;Charles;Prim. Care,2020
3. The cardiovascular–renal link and the health burden of kidney failure;Zoccali;Eur. Heart J.,2023
4. Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in innate immunity?;Bacchetta;Pediatr. Nephrol.,2013
5. Kadatane, S.P., Satariano, M., Massey, M., Mongan, K., and Raina, R. (2023). The Role of Inflammation in CKD. Cells, 12.