In individuals with CKD, uremic toxins elevate AhR levels and may provoke the accumulation of AhR-ARNT complexes while inhibiting the formation of HIF-α-ARNT complexes in the nucleus, leading to abnormal intracellular HIF signal transduction and the transition of renal interstitial EPO-producing tissues into a pathological fibrotic state associated with impaired EPO production capacity (Souma et al., 2013, 2016; Mascanfroni et al., 2015). Here, ARNT is linked to chronic kidney disease.