FGF23 in Acute and Chronic Illness

Figure 3

Hypothesis to reconcile the seemingly paradoxical effects of FGF23 and vitamin D on survival in CKD. Reproduced with permission from Wolf [15]. Baseline and change in FGF23 levels are plotted against time among 6 hypothetical patient groups. The spectrum of risk of mortality associated with FGF23 is demonstrated by the red background gradient (higher risk is darker red). Dashed lines represent active vitamin D treated groups, and solid lines represent untreated groups. “X” connotes death. The known effect of elevated baseline FGF23 on risk of mortality is represented by the higher baseline FGF23 and earlier mortality among groups 1–3 versus 4–6. The main effect of active vitamin D therapy on survival is represented by the longer survival of groups 1 and 5 versus 2 and 6. In all groups, FGF23 levels increase with longer duration of ESRD, but the rate of increase is greater among those treated with active vitamin D (greater slopes of FGF23 in groups 1 and 4 versus 2 and 3 and 5 versus 6). The hypothesized interaction between active vitamin D treatment and FGF23 is represented by the significantly greater slopes of increase in FGF23 among active vitamin D treated groups who die sooner compared with those who survive longer (crossing lines of groups 4 versus 3). Thus, it is hypothesized that survival is longest in group 5, which had low baseline FGF23 and received active vitamin D therapy but experienced only a modest increase in FGF23 in response.