Abstract
Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD.
Highlights
For a long time, phosphate, especially when its concentrations are relatively high, is recognized as a potential toxic substance for human health [1]
Experimental data have shown that fibroblast growth factor 23 (FGF23) can have a direct effect on the heart, by inducing left ventricular hypertrophy (LVH) [32,33], and pathologically interfering with calcium fluxes in cardiomyocytes out of and into the sarcoplasmic reticulum [34,35], both effects not depending on phosphate
This would be in line with the concept that FGF23 may be a mediator of phosphate toxicity, at least on the heart in a setting of chronic kidney disease (CKD) [36], and in that scenario targeting FGF23 by any means, besides addressing hyperphosphatemia, would be beneficial
Summary
Phosphate, especially when its concentrations are relatively high, is recognized as a potential toxic substance for human health [1]. Phosphate binders, phosphate transport inhibitors, controlling efforts to control serum phosphate concentrations, many patients on dialysis still do not reach treatment hyperparathyroidism, restricted use of (high dosed) active vitamin D, and adapting dialysis schemes targets [8], and a treatment gap exists This gap is an acknowledged unmet clinical need, which is if applicable, have been reviewed recently and are beyond the scope of this review [7]. Despite these addressed medication adaptingmany phosphate types,still using combination efforts by to increasing control serum phosphatedoses, concentrations, patientsbinder on dialysis do not reach therapy, intensifying dialysis schemes, and reevaluation by dietitians of intake of phosphate treatment targets [8], and a treatment gap exists.
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