The intricate interplay between systemic factors, such as mineral metabolism regulators like FGF23, PTH, and calcitriol, and intrinsic bone mechanisms, including transcription factors like HNF4α, TGF-β1, and sclerostin, highlights the complexity of CKD-associated MBD (Figure 1). This evidence concerns the gene HNF4A and Marchiafava-Bignami disease.