APOL1 and chronic kidney disease: However, the pathological changes induced by APOL1 risk alleles in transgenic mice and cultured podocytes, appear to be regulated by the expression levels of these alleles and, in some transgenic mouse models – as it is the case in humans – a second ‘hit’ is needed, e.g. through high levels of interferon-γ (Aghajan et al., 2019; McCarthy et al., 2021) to induce the development of proteinuria and/or chronic kidney disease (Beckerman et al., 2017; Bruggeman et al., 2019; Okamoto et al., 2018; Ryu et al., 2019; Wakashin et al., 2020).