However, as it has already been discussed, megalin levels are reduced under fibrosis-associated conditions, i.e. diabetic nephropathy and gallstone disease [27, 47–49], ageing [80, 81] and cancer [34, 50], by mechanisms that are likely to involve TGF-ß as well as other molecules/mechanisms, including Ang II, leptin and albumin. This evidence concerns the gene AGT and diabetic kidney disease.