Intact FGF23 predicts serum phosphate improvement after combined nicotinamide and phosphate binder treatment in hemodialysis patients

• Published in: Clinical kidney journal 2023-10, Vol.16 (10), p.1622-1633
• Main Authors: Egli-Spichtig, Daniela, Hamid, Ahmad Kamal, Arroyo, Eva Maria Pastor, Ketteler, Markus, Wiecek, Andrzej, Rosenkranz, Alexander R, Pasch, Andreas, Lorenz, Horst, Hellmann, Burkhard, Karus, Michael, Ammer, Richard, Rubio-Aliaga, Isabel, Wagner, Carsten A
• Format: Article
• Language: English
• Subjects: Calcium carbonate; Fibroblast growth factors; Health aspects; Hemodialysis; Inflammation; Medical research; Medicine, Experimental; Mortality; Niacinamide; Original; Parathyroid hormone; Phosphates; Physiological aspects
• ISSN: 2048-8505; 2048-8513
• DOI: 10.1093/ckj/sfad040

Background Hyperphosphatemia is associated with increased mortality and cardiovascular morbidity of end-stage kidney failure (ESKF) patients. Managing serum phosphate in ESKF patients is challenging and mostly based on limiting intestinal phosphate absorption with low phosphate diets and phosphate binders (PB). In a multi-centric, double-blinded, placebo-controlled study cohort of maintenance hemodialysis patients with hyperphosphatemia, we demonstrated the efficacy of nicotinamide modified release (NAMR) formulation treatment in addition to standard PB therapy in decreasing serum phosphate. Here we aimed to assess the relationship between phosphate, FGF23, inflammation and iron metabolism in this cohort. Methods We measured the plasma concentrations of intact fibroblast growth factor 23 (iFGF23) and selected proinflammatory cytokines at baseline and Week 12 after initiating treatment. Results We observed a strong correlation between iFGF23 and cFGF23 (C-terminal fragment plus iFGF23). We identified iFGF23 as a better predictor of changes in serum phosphate induced by NAMR and PB treatment compared with cFGF23. Recursive partitioning revealed at baseline and Week 12, that iFGF23 and cFGF23 together with T50 propensity were the most important predictors of serum phosphate, whereas intact parathyroid hormone (iPTH) played a minor role in this model. Furthermore, we found serum phosphate and iPTH as the best predictors of iFGF23 and cFGF23. Sex, age, body mass index, and markers of inflammation and iron metabolism had only a minor impact in predicting FGF23. Conclusion Lowering serum phosphate in ESKF patients may depend highly on iFGF23 which is correlated to cFGF23 levels. Serum phosphate was the most important predictor of plasma FGF23 in this ESKF cohort. Lay Summary Patients with end-stage kidney failure (ESKF) have a higher mortality and cardiovascular disease risk than the normal population in part due to hyperphosphatemia. Phosphate binders and nicotinamide help to control hyperphosphatemia in ESKF patients. Here we examined how the hormone fibroblast growth factor 23 (FGF23), phosphate, markers of iron metabolism and inflammation correlate in patients treated for 12 weeks with a novel formulation of nicotinamide. We demonstrate that intact and cleaved forms of FGF23 correlate tightly and had a similar capability to predict phosphate levels. Markers of iron metabolism or inflammation had only weak correlations with FGF23 or phosphate. Our data are con