This hypothesis is supported by evidence from animal experimental models and clinical observations, which show increased heparanase levels associated with HS loss in various proteinuric diseases, including diabetic nephropathy, MCD, IgA nephropathy, lupus nephritis, and membranous nephropathy (Lever et al. 2014; Rops et al. 2004; Tamsma et al. 1994; van den Born et al. 1992, 1993). This evidence concerns the gene HPSE and IgA glomerulonephritis.