Whether FGF23 is simply a disease severity marker or directly contributes to adverse outcomes is a key question that could not be answered by either previous or present observational studies; but in addition to endothelial damage, other possible mechanisms explaining the acute adverse effects of FGF23 on renal function include: immune dysfunction [25], inflammation [26] and via inhibitory effects on vitamin D metabolite activation [31]. The gene discussed is FGF23; the disease is immune system disorder.