The review discusses some of the causes of proteinuria in nephrotic syndrome due to extrarenal mechanisms. Autoantibodies identified in recent years are involved in the violation of the selective permeability of the filtration barrier in membranous nephropathy. The direct relationship between the level of hyperglycemia and proteinuria in diabetic nephropathy is analyzed. The role of reactive oxygen species, end products of glycation, angiotensin II, transforming growth factor β-1, epithelial-mesenchymal transformation of podocytes, Rho GTPases, intracellular signaling pathway mTOR, Wnt/β-catenin signaling cascade is emphasized. Particular attention is paid to the problem of searching and identifying circulating permeability factors in the pathogenesis of idiopathic nephrotic syndrome in patients with minimal changes and focal segmental glomerulosclerosis: vascular permeability factor (VPF), vasodilator-stimulated phosphoprotein (VASP), soluble hemopexin (Hpx) receptor-receptor-receptor type (suPAR), cardiotropin-like cytokine-1 (CLCF-1) and anti-CD40 antibodies. It is noted that the role of such factors is not in doubt today, however, from the standpoint of evidence-based medicine, this role needs serious confirmation by specially formulated criteria.