KCNJ10 and EAST syndrome: In summary, the disturbed Na+ and K+ handling in EAST/SeSAME syndrome thus results from defects in at least two nephron segments (Wang et al., 2018; Zhang et al., 2018, 2021; Wu et al., 2019a,b): (i) a major consequence of the Kir4.1 defect is the impaired function of the DCT, which leads to flooding of the CS with NaCl due to decreased NCC-mediated NaCl reabsorption.